ENDOCRINOLOGY AND NUTRITION

OPT 627

(SECTION A)

BY

PROF MRS. F.K. IDU

MAY 2023

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INTRODUCTION

The functions of the body are regulated by two major systems, the nervous system and the endocrine

system. The nervous system coordinates rapid and precise responses to stimuli using action potentials.

The endocrine system maintains homeostasis and long-term control using chemical signals. The

endocrine system works in parallel with the nervous system to control growth and maturation along with

homeostasis.

The events in the nervous system are rapid and finely graded as they involve electrical transmission of

impulses. In general, the events in the hormonal system are slow and generalized. The hormonal system

is concerned principally with control of metabolic functions of the body. Many inter relationship exist

between the hormonal system and the nervous system, at least two glands secrete their hormones almost

entirely in response to appropriate neural stimuli. These are the adrenal medulla and pituitary glands,

Endocrinology is the study of the characteristics and functions of ductless glands. The endocrine

system is a collection of ductless glands that secrete chemical messengers called hormones. These

signals are passed through the blood to arrive at a target organ, which has cells possessing the

appropriate receptor. Exocrine glands on the other hand secrete products that are passed outside the

body. Sweat glands, salivary glands, and digestive glands are examples of exocrine glands.

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The roles of hormones in selecting target cells and delivering the hormonal message

HORMONES

A hormone is a chemical substance or messenger that is secreted into the body fluid by one cell or a

group of cells that has a physiological control or effect on other cells of the body.

There are endocrine hormones and tissue hormone. The typical mode of cell signaling in the endocrine

system is endocrine signaling. Endocrine hormones are released and transported to act at a distance.

However, there are also other modes, i.e., paracrine, autocrine, and neuro endocrine signaling. Purely

neurocrine signaling between neurons, on the other hand, belongs completely to the nervous system.

Autocrine
Autocrine signaling is a form of signaling in which a cell secretes a hormone or chemical messenger

(called the autocrine agent) that binds to autocrine receptors on the same cell, leading to changes in the

cells. Autocrine hormones therefore act on cellular membrane that produced it.

Paracrine
Paracrine signaling is a form of cell signaling in which the target cell is near the signal-releasing cell,

altering the behavior or differentiation of those competent cells. Paracrine hormones therefore acts in

the vicinity of its release.

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Neurocrine

Neurocrine signaling is purely in the nervous system. A Neurocrine hormones is

produced by a neuron and acts near to or a distance from the neuron that released it.

Juxtacrine
Juxtacrine signaling is a type of intercellular communication that is transmitted via oligosaccharide,

lipid, or protein components of a cell membrane, and may affect either the emitting cell or the

immediately adjacent cells.

PROPERTIES OF A HORMONE

1. They are generally transported by bloodstream usually bound to carriers which are usually plasma

proteins e.g albumin, globulin etc.

2. They have different chemical structures and are classified into 3 main groups.

Steroid and related hormones, Peptide and glycoprotein hormones, amines or hormones derived from

amino acid tyrosine

Steroids

Steroids are lipids derived from cholesterol. Testosterone is the male sex hormone. Estradiol, similar in

structure to testosterone, is responsible for many female sex characteristics. Steroid hormones are

secreted by the gonads, adrenal cortex, and placenta.

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Steroid hormones are derived from cholesterol by a biochemical reaction series. Defects along this series

often lead to hormonal imbalances with serious consequences.

Peptides

Peptides are short chains of amino acids; most hormones are peptides. They are secreted by the pituitary,

parathyroid, heart, stomach, liver, and kidneys.

Peptide hormones are synthesized as precursor molecules and processed by the endoplasmic

reticulum and Golgi where they are stored in secretory granules. When needed, the granules are

deposited into the bloodstream.

Amines

Amines are derived from the amino acid tyrosine and are secreted from the thyroid and the adrenal

medulla. Solubility of the various hormone classes varies. Amine hormones (notably epinephrine) are

stored as granules in the cytoplasm until needed.

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3. Hormones are mostly inactivated in the liver and kidney. Specific receptors in the target tissues

contribute very little to the inactivation of the hormones

GENERAL FUNCTIONS OF THE ENDOCRINE SYSTEM

1. Control of the digestive tract and its accessories e.g glucagon, insulin e.t.c

2. Control of energy production i.e regulation of metabolism. It involves storage, mobilization, inter

conversion and the utilization of the various metabolic fuels to permit continued survival. Examples

of such hormone are insulin, glucagon, epinephrine, growth hormone, cortisol, thyroxine etc.

3. Control of composition and volume of Extracellular fluid. Examples are Antidiuretic hormone,

ACTH, cortisol, thyrocalcitonin, parathyroid hormone.

4. Adaptation to hostile environment by skin colouration, resistance to infection and acclimatization to

cold e.g adrenal gland hormones, thyroid hormones.

5. Control of growth, maturation and development eg Growth hormone.

6. Important in survival of the species i.e reproduction. Examples are sex hormones, FSH,

progesterone, Estrogen, LH etc.

MECHANISM OF ACTION OF HORMONES

The endocrine system acts by releasing hormones that in turn trigger actions in specific target cells. A

hormone affects the target tissues by first activating target receptors in the tissue cells. Receptors on

target cell membranes bind only to one type of hormone. The binding hormone changes the shape of the

receptor causing the response to the hormone. There are two mechanisms of hormone action on all target

cells.

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Receptor

It is hypothetical unique molecular grouping in or on a cell that interacts with a hormone in a highly

specific manner such that a characteristic response or group of responses is elicited.

Generally, hormones are thought to act on the receptor via one of these mechanisms.

1. Direct Membrane Effect

This is mostly related to the alteration of the structure of the membrane e.g. opening of pores,

influencing the activities of some sort of carriers or activating a pump. e.g neurotransmitters,

aldosterone.

2. Intracellular 2nd Messenger Theory

Non steroid hormones (water soluble) do not enter the cell but bind to plasma membrane receptors,

generating a chemical signal (second messenger) inside the target cell. Five different second

messenger chemicals, including cyclic AMP have been identified. Second messengers activate other

intracellular chemicals to produce the target cell response.

The hormones itself is taken as the 1st messenger which on getting to the receptor of the membrane

surface activates cytoplasmic systems which is the 2nd messenger that results in the activation of

various kinases.

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 Steps in the action of nonsteroid hormones

3. Intracellular Protein Synthesis Theory

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This mechanism involves steroid hormones, which pass through the plasma membrane and act in a

two step process. Steroid hormones bind, once inside the cell, to the nuclear membrane receptors,

producing an activated hormone-receptor complex. The activated hormone-receptor complex binds

to DNA and activates specific genes, increasing production of proteins.

Steps in the action of steroid hormones

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REGULATION OF HORMONE SECRETION

The endocrine system uses cycles and negative feedback to regulate physiological functions. Negative

feedback regulates the secretion of almost every hormone. Cycles of secretion maintain physiological

and homeostatic control. These cycles can range from hours to months in duration.

The feedback mechanism means that the hormone produces a biological effect that on attaining a

sufficient magnitude inhibits further secretion.

The negative feedback is as follows:-

The endocrine gland has a natural tendency to over secrete its hormones and because of this, the

hormone exerts more and more of its control effect on the target organ. The target organ on its own

performs its function but when too much function occurs, usually some factors about the function feeds

back to the endocrine gland and carries a negative effect to the gland to decrease its secretory rate . Thus

the function of the hormone is monitored and this information in turn provides a negative feedback

control on the secretary rate of the gland. The important factor to be controlled usually is not the

secretary rate but the degree of activity of the target organ. Therefore only when target organ activity

rises to an appropriate level will a feedback effect be powerful enough to slow down further secretion of

the hormone.

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 Negative feedback in the thyroxine release reflex.

POSITIVE FEEDBACK MECHANISM

In positive feedback, the hormone upon attaining its biological activity stimulate further secretion of

itself thus enhancing its biological activity e.g oxytocin release during breast feeding and labour, and

Positive Feedback Effect of Estrogen before Ovulation.

Estrogen

During the female reproductive cycle, ovarian estradiol exerts negative feedback to reduce gonadotropin

release. However, in the late follicular phase (2 days before ovulation), and in response to sustained high

levels of estradiol from preovulatory follicles, the action of estradiol switches from negative to positive

feedback, resulting in a surge release of GnRH. The GnRH surge triggers a surge of LH secretion. The

secreted LH then acts on the ovaries to stimulate an additional secretion of estrogen, which in turn

causes more secretion of LH to initiate ovulation.

Oxytocin in labour

As labor begins, the cervix of the uterus is stretched, which generates sensory impulses to the

hypothalamus, which in turn stimulates the posterior pituitary to release oxytocin. Oxytocin produces

more powerful uterine contractions so that the fetus is pushed more forcefully against the cervix,

stimulating more oxytocin release in a continuous positive feedback cycle.

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 Oxytocin in milk ejection

After labor, release of milk at the nipple stimulates the baby to start suckling vigorously, which

stimulates the receptors in the nipple even more, so that there is even more oxytocin released from the

maternal pituitary and even more milk is released and so on, until the baby is satiated and unlatches

from the breast, when everything goes back to normal. This is a positive feedback mechanism

PRINCIPAL ENDOCRINE GLANDS OF THE BODY AND THEIR HORMONES

HYPOTHALAMUS

SECRETED
ABBREVIATION PRODUCED BY EFFECT
HORMONE

Stimulate thyroid-stimulating
Thyrotropin- Parvocellular neurosecretory
TRH hormone (TSH) release
releasing hormone neurons
fromanterior pituitary (primarily)

Dopamine
(Prolactin- Dopamine neurons of the Inhibit prolactin released
DA or PIH
inhibiting arcuate nucleus from anterior pituitary
hormone)

Stimulate Growth hormone

Growth hormone- Neuroendocrineneurons of
GHRH (GH) release from anterior
releasing hormone theArcuate nucleus
pituitary

Somatostatin SS, GHIH, or SRIF Neuroendocrine cells of Inhibit Growth hormone

(growth hormone- the Periventricular nucleus (GH) release from anterior
inhibiting pituitary
hormone) Inhibit thyroid-stimulating
hormone (TSH) release

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 fromanterior pituitary

Stimulate follicle-stimulating
hormone (FSH) release
Gonadotropin- Neuroendocrine cells of fromanterior pituitary
GnRH or LHRH
releasing hormone the Preoptic area Stimulate luteinizing hormone
(LH) release from anterior
pituitary

Parvocellular neurosecretory Stimulate adrenocorticotropic

Corticotropin-
CRH or CRF neurons of theParaventricular hormone (ACTH) release from
releasing hormone
Nucleus anterior pituitary

Magnocellular neurosecretory
neurons of theSupraoptic Uterine contraction
Oxytocin OT or OXT
nucleusand Paraventricular Lactation (letdown reflex)
nucleus

Parvocellular neurosecretory Increases water permeability in

Vasopressin neurons,Magnocellular the distal convoluted tubule and
(antidiuretic ADH or AVP or VP neurosecretory neurons of collecting duct of nephrons, thus
hormone) theParaventricular promoting water reabsorption and
nucleus andSupraoptic nucleus increasing blood volume

ANTERIOR PITUITARY( ADENOHYPOPHYSIS)

SECRETED
ABBREVIATION FROM CELLS EFFECT
HORMONE

Growth hormone GH Somatotrophs Stimulates growth and cell reproduction

(somatotropin) Stimulates Insulin-like growth factor

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 1 release from liver

Stimulates thyroxine (T4)

Thyroid-
and triiodothyronine (T3) synthesis and
stimulating
TSH Thyrotrophs release from thyroid gland
hormone
Stimulates iodine absorption by thyroid
(thyrotropin)
gland

Stimulates corticosteroid (glucocorticoid a

Adrenocorticotro
ndmineralcorticoid)
pic hormone ACTH Corticotrophs
and androgen synthesis and release
(corticotropin)
fromadrenocortical cells

Beta-endorphin - Corticotrophs Inhibits perception of pain

In females: Stimulates maturation

of ovarian follicles in ovary
In males: Stimulates maturation
Follicle-
of seminiferous tubules
stimulating FSH Gonadotrophs
In males: Stimulates spermatogenesis
hormone
In males: Stimulates production
of androgen-binding proteinfrom Sertoli
cells of the testes

In females: Stimulates ovulation

In females: Stimulates formation of corpus
Luteinizing
LH Gonadotrophs luteum
hormone
In males: Stimulates testosterone synthesis
from Leydig cells (interstitial cells)

Stimulates milk synthesis and release

Prolactin PRL Lactotrophs from mammary glands
Mediates sexual gratification

Melanocyte- MSH Melanotropes in Stimulates melanin synthesis and release

stimulating thePars from skin/hairmelanocytes
hormone intermedia of the

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 Anterior
Pituitary

POSTERIOR PITUITARY LOBE (NEUROHYPOPHYSIS)

SECRETED
ABBREVIATION FROM CELLS EFFECT
HORMONE

Uterine contraction
Magnocellular
Oxytocin Lactation (letdown
neurosecretory cells
reflex)

Increases water
permeability in the
distal convoluted
Vasopressin tubule and collecting
Parvocellular
(antidiuretic ADH or AVP duct of nephrons, thus
neurosecretory neurons
hormone) promoting water
reabsorption and
increasing blood
volume

THYROID GLAND

SECRETED FROM
ABBREVIATION EFFECT
HORMONE CELLS

Triiodothyronine T3 Thyroid (More potent form of thyroid

epithelial cell hormone)
Stimulates body oxygen and energy
consumption, thereby increasing

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 the basal metabolic rate
Stimulates RNA polymerase I and II,
thereby promotingprotein synthesis

(Less active form of thyroid hormone)

(Acts as
a prohormone to triiodothyronine)
Thyroid
Thyroxine Stimulates body oxygen and energy
T4 epithelial
(tetraiodothyronine) consumption, thereby increasing
cells
the basal metabolic rate
Stimulates RNA polymerase I and II,
thereby promotingprotein synthesis

Stimulates osteoblasts and thus bone

Parafollicular construction
Calcitonin
cells Inhibits Ca2+ release from bone,
thereby reducing blood Ca2+

ADRENAL GLAND

Adrenal cortex

Secreted hormone From cells Effect

Stimulates gluconeogenesis
Stimulates fat breakdown in
adipose tissue
Inhibits protein synthesis
zona
Inhibits glucose uptake in muscle
Glucocorticoids (chieflycortisol) fasciculata and zona
and adipose tissue
reticularis cells
Inhibits immunological responses
(immunosuppressive)
Inhibits inflammatory responses
(anti-inflammatory)

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 Stimulates
active sodium reabsorption
in kidneys
Stimulates passive water
Zona reabsorption in kidneys, thus
Mineralocorticoids (chieflyaldosterone)
glomerulosa cells increasing blood
volume and blood pressure
Stimulates potassium and H+ secr
etion into nephron of kidney and
subsequent excretion

In males: Relatively small effect

Zona
Androgens (including DHEAand testosterone compared to androgens from
fasciculata and Zona
) testes
reticularis cells
In females: masculinizing effects

ADRENAL MEDULLA

SECRETED HORMONE FROM CELLS EFFECT

Fight-or-flight response:

 Boost the supply of oxygen and glucose to

the brain andmuscles (by increasing heart
rate and stroke volume,vasodilation,
Adrenaline (epinephrine)
Chromaffin cells increasing catalysis of glycogen in liver,
(Primarily)
breakdown of lipids in fat cells)
 Dilate the pupils

 Suppress non-emergency bodily processes

(e.g., digestion)

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 Fight-or-flight response:

 Boost the supply of oxygen and glucose to

the brain andmuscles (by increasing heart
Noradrenaline(norepinephrine) Chromaffin cells rate and stroke volume,vasoconstriction and
increased blood pressure, breakdown
oflipids in fat cells)

 Increase skeletal muscle readiness.

Dopamine Chromaffin cells Increase heart rate and blood pressure
Enkephalin Chromaffin cells Regulate pain

HYPOTHALAMUS

The hypothalamus is located in the lower central part of the brain below the thalamus. It is important in

regulation of satiety, metabolism, and body temperature. It is also a glandular tissue. Synaptic input as

well as spontaneous neuronal activities within the hypothalamus can stimulate the release of hormones.

It secretes hormones that stimulate or suppress the release of hormones in the pituitary gland. Many of

these hormones are releasing hormones, which are secreted into an artery (the hypophyseal portal

system) that carries them directly to the pituitary gland. In the pituitary gland, these releasing hormones

signal secretion of stimulating hormones. The hypothalamus also secretes hormones called somatostatin

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and prolactostatin, which cause the pituitary gland to stop the release of growth hormone and prolactin

respectively.

All the hormones released from the hypothalamus are peptides except prolactin inhibiting hormone

which is a tyrosine derivative. These hormones in modern terminology have the suffix “liberin”

meaning “releasing”and “statin” meaning ‘inhibiting’

Function of the releasing and inhibiting hormones of the Hypothalamus.

The function is to control the secretion of anterior pituitary hormones. For most of the ant. pituitary, it is

the releasing hormones that are important but for prolactin, an inhibiting hormone probably exerts more

control. The hypothalamic inhibitory and releasing hormones that are of major importance are as

follows.

1. Somatoliberin, Growth hormone releasing hormone (GHIH).

2. Thyroliberin, Thyrotropin Releasing Hormone(TRH) which causes the release of thyroid

stimulating hormone

3. Corticoliberin, Corticotropin releasing hormone (CRH) causes the release of ACTH

4. Gonadoliberin (Gonadotrophin releasing hormone) causes the release of two gonadotrophic hormone

i.e LH and FSH.

5. Melanoliberin melanocyte Releasing hormone (MRH) causes release of melanocyte stimulating

hormone.

6. Prolactoliberin, Prolactin releasing hormone (PRH) stimulates the secretion of prolactin.

7. Prolactostatin, Prolacting inhibiting hormone (PIH) causes the inhibition of prolactin secretion.

8. Somatostatin (Growth Hormone inhibiting hormone). Inhibits the release of growth hormone.

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THE PITUITARY GLAND

The pituitary gland is located at the base of the brain beneath the hypothalamus. It is a small gland about

1cm in diameter and weighs about 0.5g in man. It is often considered the most important part of the

endocrine system because it produces hormones that control many functions of other endocrine glands.

When the pituitary gland does not produce one or more of its hormones or not enough of them, it is

called hypopituitarism. The pituitary gland is also called the Hypophysis. It is connected with the

hypothalamus by the pituitary or hypophyseal stalk. It is made up of two parts which are

embryologically different. The anterior pituitary (adenohypophysis) and the posterior pituitary

(neurohypophysis). The two parts are derived embryologically from two different parts of the body. The

posterior pituitary is a nervous tissue derived from the down growth of the brain. The anterior Pituitary

is in an up growth of the mouth called the RAPHE’S POUCH.

The anterior pituitary is supplied by the hypothalamo-hypophyseal portal vessels. Whereas the posterior

pituitary is supplied by the hypothalamo hypophyseal tract.

The anterior lobe produces the following hormones, which are regulated by the hypothalamus:

Growth hormone: Stimulates growth of bone and tissues.

Thyroid-stimulating hormone (TSH): Stimulates the thyroid gland to produce thyroid hormones.

Adrenocorticotropin hormone (ACTH): Stimulates the adrenal gland to produce several related

steroid hormones

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH): Hormones that control sexual

function and production of the sex steroids, estrogen and progesterone in females or testosterone in

males

Prolactin: Hormone that stimulates milk production in females.

Melanocyte stimulating Hormone :

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The posterior lobe produces the following hormones, which are not regulated by the hypothalamus:

Antidiuretic hormone (vasopressin): Controls water loss by the kidneys.

Oxytocin: Contracts the uterus during childbirth and stimulates milk production.

Anterior Pituitaryhormones that act on no specific endocrine organs.

 Growth Hormone

 Prolactin

 Melanocyte stimulating hormone

Anterior pituitary hormones that act on specific endocrine organs.

 Adrenocorticotrophin (ACTH)

 Thyroid stimulating hormone (TSH)

 Gonadotropic hormones (FSH, LH)

CONTROL OF PITUITARY SECRETION BY THE HYPOTHALAMUS

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Hypothalamic-hypophysial axis

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 Relationship between anterior pituitary and hypothalamus

Almost all secretions by the pituitary are controlled by either hormonal or nervous signals from the

hypothalamus. All or most of the hypothalamic hormones are secreted at nerve endings in the median

eminence before being transported to anterior pituitary gland. Electrical stimulation of this region

excites these nerve endings and therefore causes release of essentially all the hypothalamic hormones.

The secretion by the ant. Pituitary is controlled by the hormone called hypothalamic releasing or

inhibitory hormones which are synthesized and secreted by special neurons in the hypothalamus. These

hormones are immediately absorbed into hypothalamic-hypophysial portal system carried to sinuses of

the ant. Pituitary gland after being secreted by the fibres of these special neurones.

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HYPOTHALAMUS AND POSTERIOR PITUITARY GLAND

Relationship between hypothalamus and posterior pituitary

The relationship between hypothalamus and posterior pituitary is in the neural connection, the

hypothalamo-hypophysial tract. These neurones originate in various parts of the hypothalamus

including the Supraoptic (SON) and the Paraventicular (PVN) nuclei and send their nerve fibres into

the median eminence and tubercinerum an extension of hypothalamic tissue that extends into the

pituitary stalk. These fibres terminate in the posterior Pituitary.

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GROWTH HORMONE

Growth hormone (GH or HGH), also known as somatotropin or somatropin, is a peptide hormone that

stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is

a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by somatotropic

cells within the lateral wings of the anterior pituitary gland.

The normal concentration of GH in plasma of an adult is 1.5-3.0ng/mL and in a child or adolescent it is

about 6.0ng/mL. However these values often increase to as high as 50ng/mL after the body depletion of

stores of protein or carbohydrate.

Somatotropic cells in the anterior pituitary gland synthesize and secrete GH in a pulsatile manner, in

response to the stimuli of somatoliberin and somatostatin by the hypothalamus. The largest and most

predictable of these GH peaks occurs about an hour after onset of sleep with plasma levels of 13 to

72 ng/mL. Otherwise there is wide variation between days and individuals. Nearly fifty percent of GH

secretion occurs during the third and fourth NREM sleep stages. Surges of secretion during the day

occur at 3- to 5-hour intervals. The plasma concentration of GH during these peaks may range from 5 to

even 45 ng/mL.

Regulation of secretion

Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of

the hypothalamus. These cells release the peptides Growth hormone-releasing hormone (GHRH

or somatoliberin) and Growth hormone-inhibiting hormone (GHIH or somatostatin) into

the hypophyseal portal venous blood surrounding the pituitary. GH release in the pituitary is primarily

determined by the balance of these two peptides, which in turn is affected by many physiological

stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion.

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A number of factors are known to affect GH secretion, such as age, gender, diet, exercise, stress, and

other hormones. Young adolescents secrete GH at the rate of about 700 μg/day, while healthy adults

secrete GH at the rate of about 400 μg/day. Sleep deprivation generally supresses GH release,

particularly after early adulthood.

Stimulators of growth hormone (GH) secretion include:

 peptide hormones GHRH (somatoliberin) through binding to the growth hormone-releasing

hormone receptor (GHRHR)

 sex hormones, increased androgen secretion during puberty (in males from testis and in females

from adrenal cortex).

estrogen

 hypoglycemia

 deep sleep

 fasting

 vigorous exercise

Inhibitors of GH secretion include:

 GHIH (somatostatin) from the periventricular nucleus

 circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus)

 hyperglycemia

 glucocorticoids

 dihydrotestosterone

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GH in contrast with other hormones does not function through a target gland but instead exerts its

effect on almost all tissues of the body.

Specific effects of Growth hormone

Effects of growth hormone on the tissues of the body can generally be described as anabolic (building

up). Like most other protein hormones, GH acts by interacting with a specific receptor on the surface of

cells.

1. Effect on growth

It causes the growth of almost all tissues of the body that are capable of growing. It promotes increased

size of the cells, by increased mitosis with development of increased number of cells and specific

differentiation of certain types of cells such as bone growth cells and early muscle cells. Increased

height during childhood is the most widely known effect of GH.

Formation of cartilage is accelerated resulting in linear growth, the excess of which can result in

gigantism.

Most of the effects of the GH on cartilage are indirect and are mediated by somatomedins (small

peptides released from the liver by GH) It is involved in osteogenesis. In this regard when the epiphysis

are closed, GH stimulation results in acromegaly (over growth of soft tissues resulting in enlarged feet

and hands). The size and general functions of most organs in the body are increased. In hypo function of

GH dwarfism result.

2. Effect on metabolism

Aside its general effect in causing growth, GH has many specific metabolic effects as well, these

include:

(a) Effect on Carbohydrate metabolism

1. Decreases use of glucose for energy

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2. Enhances glycogen deposition in the cells

3. Diminishes uptake of glucose by cells but promotes gluconeogenesis in the liver

4. Increases insulin secretion and decreases sensitivity to insulin. It is diabetogenic and indeed may

intensify the severity of clinical diabetes in the human subject.

(b) Effect on Fat Metabolism

(i) Has a specific effect in causing the release of fatty acids in body fluids.

(ii) Enhances the conversion of fatty acids to acetyl co-enzyme A (Acetyl Co A) with subsequent

utilization of this for energy.

(iii) Ketogenic effect. Under the effect of excessive amount of GH fat mobilization from adipose

tissues can sometimes become so great large quantity of acetoacetic acid are formed by the liver

and released into the body fluids causing ketosis

(c) Effects on Protein Metabolism

GH enhances almost all processes of amino acid up take, protein synthesis (anabolism) by cells while at

the same time reducing the breakdown (catabolism) of protein synthesis. It does this by:

- Enhancement of amino acid transport through all membrane.

- Enhancement of RNA translocation to promote protein synthesis by the ribosomes

- Increased nuclear transcription of DNA to form RNA

- Decreased catabolism of protein and amino acid

3. Effect on Electrolytes

It reduces plasma urea levels but increases phosphorous levels. It also increased calcium

reabsorption by the GIT.

Abnormalities of GH

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DEFICIENCY

The effects of growth hormone deficiency vary depending on the age at which they occur. In

children, growth failure and short stature are the major manifestations of GH deficiency, with common

causes including genetic conditions and congenital malformations. It can also cause delayed sexual

maturity. In adults, deficiency is rare.

Dwarfism – Most instances of dwarfism results from generalized insufficiency of anterior pituitary

secretion during childhood. In general, the features of the body develop in appropriate proportion to

each other but the rate of development is greatly reduced.

EXCESS

Gigantism – Occasionally, the somatotropic or acidophilic GH producing cells of the ant. Pituitary

becomes excessively active, as a result, large quantities of GH are produced. All body tissues grow

rapidly including the bones. If the condition occurs by adolescence i.e before the epiphyses of the long

bone become fused with the shaft, height increases so that the person becomes a giant ( 8 - 9ft ) tall.

1. Acromegaly – If an acidophilic tumour occurs after adolescence i.e after the epiphysis are fused,

the person cannot grow taller but the soft tissues can continue to grow and the bones can grow in

thickness. Prolonged GH excess thickens the bones of the jaw, fingers and toes. Resulting heaviness

of the jaw and increased size of digits is referred to as acromegaly.

PROLACTIN

Also known as lactogenic or mammographic hormone or luteotrophic hormone. It is a peptide produced

by the lactotropic cells of the adenohypophysis. It is also synthesized and secreted by a broad range of

other cells in the body, most prominently various immune cells, the brain and the decidua of the

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pregnant uterus. It is similar to GH in its size and amino acid composition. Although produced in both

sexes, the plasma level in males is very low.

The normal values for prolactin are:

 Males: 2 - 18 ng/mL

 Nonpregnant females: 2 - 29 ng/mL

 Pregnant women: 10 - 209 ng/mL

Physiologic effects of prolactin

Mammary Gland Development, Milk Production and Reproduction:

The major target organ of prolactin is the mammary [Link] primary action of prolactin is that it acts

directly on milk secreting cells of the mammary tissue to develop the gland an well as to cause milk

production.

Prolactin has two major roles in milk production:

 Prolactin induces lobuloalveolar growth of the mammary gland. Alveoli are the clusters of cells

in the mammary gland that actually secrete milk. Increased serum concentrations of prolactin

during pregnancy cause enlargement of the mammary glands of the breasts and prepare for the

production of milk

 Prolactin stimulates lactogenesis or milk production after giving birth. Prolactin, along with

cortisol and insulin, act together to stimulate transcription of the genes that encode milk proteins.

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Prolactin also appears important in several non-lactational aspects of reproduction. In some species

(rodents, dogs, skunks), prolactin is necessary for maintainance of corpora lutea (ovarian structures that

secrete progesterone.

Effects on Immune Function

The prolactin receptor is widely expressed by immune cells, and some types of lymphocytes synthesize

and secrete prolactin. These observations suggest that prolactin may act as an autocrine or paracrine

modulator of immune activity

Dopamine (Prolactin inhibitory hormone) serves as the major prolactin-inhibiting factor or brake on

prolactin secretion. Dopamine is secreted into portal blood by hypothalamic neurons, binds to receptors

on lactotrophs, and inhibits both the synthesis and secretion of prolactin.

During pregnancy, high circulating concentrations of estrogen increase prolactin levels by 10- to 20-

fold. However, at the same time, estrogen, as well as progesterone, inhibit the stimulatory effects of

prolactin on milk production. It is the abrupt drop of estrogen and progesterone levels following delivery

that allows prolactin — which temporarily remains high — to induce lactation.

After childbirth, prolactin levels fall as the internal stimulus for them is removed. Sucking by the baby

on the nipple then promotes further prolactin release, maintaining the ability to lactate. The sucking

activates mechanoreceptors in and around the nipple. These signals are carried by nerve fibers through

the spinal cord to the hypothalamus, where changes in the electrical activity of neurons that regulate the

pituitary gland cause increased prolactin secretion. The suckling stimulus also triggers the release

of oxytocin from the posterior pituitary gland, which triggers milk let-down: Prolactin controls milk

production (lactogenesis) but not the milk-ejection reflex; the rise in prolactin fills the breast with milk

in preparation for the next feed.

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Abnormalities of prolactin secretion

Excessive secretion of prolactin - hyperprolactinemia - is a relatively common disorder in humans. This

condition has numerous causes, including prolactin-secreting tumors and therapy with certain drugs.

Common manifestations of hyperprolactinemia in women include amenorrhea (lack of menstrural

cycles) and galactorrhea (excessive or spontaneous secretion of milk). Men with hyperprolactinemia

typically show hypogonadism, with decreased sex drive, decreased sperm production and impotence.

Such men also often show breast enlargement (gynecomastia), but very rarely produce milk.

Sometimes, newborn babies (males as well as females) secrete a milky substance from

their nipples known as witch's milk. This is in part caused by maternal prolactin and other hormones.

Lack of prolactin does not give an obvious sign.

MELANOCYLE STIMULATING HORMONE

The melanocyte-stimulating hormones (collectively referred to as MSH or intermedins are a class

of peptide hormones that are produced by cells in the intermediate lobe of the pituitary gland. They

stimulate the production and release of melanin (melanogenesis) by melanocytes in skin and hair. MSH

disperses these melanin granules within the melanocytes of the skin especially for camouflaging in

lower animals.

An increase in MSH will cause a darkening in humans too. Melanocyte-stimulating hormone increases

in humans during pregnancy. This, along with increased estrogens, causes increased pigmentation in

pregnant women

It is structurally similar to ACTH and it also known that when ACTH is released, MSH is often secreted

along with it.

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PITUITARY HORMONES THAT ACT ON SPECIFIC TARGET ENDOCRINE ORGANS

 Adrenocorticotrophin (ACTH)

 Thyroid stimulating hormone (TSH)

 Gonadotropic hormones (FSH, LH)

ADRENOCORTICOTROPHIN (ACTH).

Adrenocorticotropic hormone (ACTH), also called corticotropin or adrenocorticotropin, is a

polypeptide hormone formed in the pituitary gland that regulates the activity of the cortex of the adrenal

glands. The half life is less than 10 minutes and therefore is rapidly inactivated.

In mammals the action of ACTH is limited to those areas of the adrenal cortex in which

the glucocorticoid hormones—cortisol and corticosterone are formed.

Actions of ACTH

The actions of ACTH on the adrenal cortex are as follows.

ACTH stimulates secretion of glucocorticoid steroid hormones from adrenal cortex cells, especially in

the zona fasciculata of the adrenal glands. ACTH acts by binding to cell surface ACTH receptors, which

are located primarily on adrenocortical cells of the adrenal cortex.

ACTH causes increase in size and weight of the adrenal glands.

Regulation of ACTH

ACTH is secreted from corticotropes in the anterior lobe (or adenohypophysis) of the pituitary gland in

response to the hormone corticotropin-releasing hormone (CRH) released by the hypothalamus.

In order to regulate the secretion of ACTH, many substances secreted within this axis exhibit

slow/intermediate and fast feedback-loop activity. Glucocorticoids secreted from the adrenal cortex

33
 work to inhibit CRH secretion by the hypothalamus, which in turn decreases anterior pituitary secretion

of ACTH.

THYROID STIMULATING HORMONE

Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a hormone that stimulates the

thyroid gland to produce thyroxine (T4), and triiodothyronine (T3) which stimulates the metabolism of

almost every tissue in the body. It is a glycoprotein hormone synthesized and secreted

by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid

gland.

Functions of TSH

The primary effect of TSH is that it stimulates every function of the thyroid gland.

 It stimulates the follicular cells to convert iodine and the amino acid tyrosine into thyroid

hormones.

 promotes the release of the hormones from the follicles and increases thyroid blood flow.

Regulation of secretion

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TSH stimulates the thyroid gland to secrete the hormone thyroxine (T4), which has only a slight effect

on metabolism. T4 is converted to triiodothyronine (T3), which is the active hormone that stimulates

metabolism. About 80% of this conversion is in the liver and other organs, and 20% in the thyroid itself.

Thyrotropin-releasing hormone(TRH) produced by the hypothalamus stimulates the pituitary gland to

produce TSH.

Somatostatin is also produced by the hypothalamus, and has an opposite effect on the pituitary

production of TSH, decreasing or inhibiting its release.

The concentration of thyroid hormones (T3 and T4) in the blood regulates the pituitary release of TSH;

when T3 and T4 concentrations are low, the production of TSH is increased, and, conversely, when

T3 and T4 concentrations are high, TSH production is decreased. This is an example of a

negative feedback loop.

GONADOTROPHIC HORMONES

Gonadotropins are protein hormones secreted by gonadotrope cells of the anterior

pituitary. This includes the mammalian hormones follicle-stimulating hormone (FSH)

and luteinizing hormone (LH).

Follicle stimulating hormone (FSH)

FSH is a glycoprotein with the following functions.

 stimulates follicular growth in the ovary in females and spermatogenesis in males.

 Stimulates oestrogen production and secretion by the ovaries (follicular cells).

 It causes ovulation in conjunction with LH.

Regulation

It is controlled by GnRH and levels of oestrogen and testosterone.

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 The increase in serum estradiol levels cause a decrease in FSH production by inhibiting GnRH

production in the hypothalamus

LUTEINIZING HORMONE

Luteinizing hormone (LH) is a hormone produced by gonadotrophic cells in the anterior pituitary

gland. In females, an acute rise of LH ("LH surge") triggers ovulation and development of the corpus

luteum. In males, it stimulates the Leydig cells to produce testosterone. It acts synergistically

with (FSH).

Functions of LH

 It induces ovulation in conjunction with FSH and promotes luteinization (formation of the

corpus luteum)

 It stimulates progesterone secretion by corpus luteum.

 In the male, it stimulates the interstitial cells of leydig to produce testosterone.

Regulation of LH

It is controlled by GnRH and levels of progesterone and testosterone.

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POSTERIOR PITUITARY HORMONES (NEUROHYPOPHYSIS)

Synthesis of posterior pituitary hormones

The posterior pituitary gland is composed mainly of glial-like cells called pituicytes. These cells do not

secrete hormones but act as supporting structure for large number of terminal nerve fibres and nerve

endings from nerve tracts that originate in the SON and PVN of the hypothalamus. The hormones

arginine vasopressin( ADH) and oxytocin are the hormones secreted by the posterior pituitary.

The hormones are initially synthesized in the cell bodies of the SON and PVN and are then transported

in combination with the carrier protein neurophysin down to the nerve endings in the post. Pit gland

requiring several days to reach the gland. Upon stimulation, these neurosecretory cells are able to release

the hormones together with the neurophysin by a process of exocytosis that involves calcium ion, but

37
because they are only loosely bound to each other, the hormone separates almost immediately. The

neurophysin has no known function after leaving the nerve terminals.

ADH is formed primarily in the SON whereas oxytocin is formed primarily in the PVN. However,

each of these two nuclei can synthesize approximately 1/6th as much of the 2 nd hormone as its primary

hormone.

Antidiuretic hormone (ADH)

Antidiuretic hormone (ADH) also known as arginine vasopressin in humans is a peptide consisting of

nine amino acids (nonapeptide) produced in the supraoptic and paraventricular nuclei of the

hypothalamus. It is synthesized in the hypothalamus and transported to the posterior pituitary. It is

transported slowly along the ‘hypothalamo-hypophyseal tract’ in combination with the carrier protein

neurophysin to the nerve terminals in the posterior pituitary where they are stored, and from where they

are secreted into the systemic circulation.

Physiologic Effects of Antidiuretic Hormone

Effects on the Kidney (Antidiuretic effect)

The single most important effect of antidiuretic hormone is to conserve body water by reducing the loss

of water in urine. A diuretic is an agent that increases the rate of urine formation. Injection of small

amounts of antidiuretic hormone into a person or animal results in antidiuresis or decreased formation of

urine, and the hormone was named for this effect.

In the absence of ADH, the collecting tubules and ducts are totally impermeable to water which

prevents significant reabsorbsion of water and therefore allows extreme loss of water into urine. On the

other hand, in the presence of ADH, the permeability of the collecting ducts and tubules to water

changes greatly allows most of the water to be reabsorbed as the tubular fluid passes through these ducts

38
thereby conserving water for the body. The stimulus for this action is a sustained increase in plasma

osmolality of about 3mmol/lit (1-2% increase).

Antidiuretic hormone stimulates water reabsorbtion by stimulating insertion of "water channels"

or aquaporins into the membranes of kidney tubules. These channels transport solute-free water through

tubular cells and back into blood, leading to a decrease in plasma osmolarity and an increase osmolarity

of urine.

Vasoconstrictor effect :

Higher concentration of ADH has a very potent effect of constricting the arteriole everywhere in the

body and therefore of increasing arterial pressure. For this reason, ADH has another name vasopressin.

One of the stimuli for causing intense ADH secretion is decreased blood volume, this occurs strongly

when the blood volume decreases 15-20% with the secreting rate then rising sometimes to 20-50 times

normal.

Regulation of ADH production

The most important variable regulating antidiuretic hormone secretion is plasma osmolarity, or the

concentration of solutes in blood. Osmolarity is sensed in the hypothalamus by neurons known as

an osmoreceptors, and those neurons, in turn, stimulate secretion from the neurons that produce

antidiuretic hormone.

Antidiuretic hormone concentrations rise steeply and linearly with increasing plasma osmolarity. When

the ECF becomes too concentrated, fluid is pulled by osmosis out of the osmoreceptor cell, decreasing

its size and initiating appropriate signal for ADH secretion. Conversely, when the ECF becomes too

dilute, water moves by osmosis in the opposite direction into the cell and this decreases the signal for

ADH secretion. Thus concentrated body fluid do stimulate the SON whereas dilute fluids inhibits them.

39
Therefore a feedback control system is available to control the total osmotic pressure of the body fluids

as follows.

- when the body fluid becomes highly concentrated, the SON becomes excited. Impulses are

transmitted to the post. Pituitary and ADH is secreted. This passes by way of the blood to the

kidneys where it increases the permeability of collecting ducts to water. As a result most of the

tubular fluid are reabsorbed while electrolytes continues to be lost into the urine. This dilutes the

ECF returning it to a reasonably normal osmotic composition.

Clinical conditions involving ADH actions

A. The most common disease of man and animals related to antidiuretic hormone is diabetes

insipidus. This is a syndrome that refers to the passing out of large amount of hyposmotic

urine, about 5L/day. Insipidus – tasteless.

The major sign of diabetes insipidus is excessive urine production. Some human patients produce as

much as 16 liters of urine per day! If adequate water is available for consumption, the disease is rarely

life-threatening.

There are 3 types of DI , depending on etiology.

i. Psychogenic Diabetes insipidus : It is caused by chronic and excessive ingestion of fluid leading

to a constant inhibition of ADH secretion.

ii. Hypothalamic Diabetes insipidus

It is caused by hypothalamic failure involving a defect in the production or release of ADH.

Hypothalamic ("central") diabetes insipidus results from a deficiency in secretion of antidiuretic

40
 hormone from the posterior pituitary. Causes of this disease include head trauma, and infections

or tumors involving the hypothalamus.

iii. Nephrogenic Diabetes insipidus

Nephrogenic diabetes insipidus occurs when the kidney is unable to respond to antidiuretic

hormone. Most commonly, this results from some type of renal disease, but mutations in the

ADH receptor gene or in the gene encoding aquaporin-2 have also been demonstrated in affected

humans.

B. The syndrome of inappropriate ADH secretion (SIADH)

In this syndrome, there is low plasma sodium (hyponatremia) and low plasma osmolality (hypo-

osmolality), stimuli that should decrease the secretion of ADH, instead the syndrome is

associated with increased ADH secretion hence the name inappropriate secretion of ADH.

OXYTOCIN

Oxytocin is a nine amino acid peptide that is synthesized in hypothalamic neurons and transported down

axons of the posterior pituitary for secretion into blood. Oxytocin is also secreted within the brain and

from a few other tissues, including the ovaries and testes. Oxytocin differs from antidiuretic hormone in

two of the nine amino acids. Both hormones are packaged into granules and secreted along with carrier

proteins called neurophysins.

Oxytocin is present in both males and females but it exerts its action in females.

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Physiologic effects of oxytocin

Stimulation of milk ejection (milk letdown): Milk is initially secreted into small sacs within the

mammary gland called alveoli, from which it must be ejected for consumption. Mammary alveoli are

surrounded by smooth muscle (myoepithelial) cells which are a prominant target cell for oxytocin.

Oxytocin stimulates contraction of myoepithelial cells, causing milk to be ejected into the ducts and

cisterns.

Stimulation of uterine smooth muscle contraction at birth: At the end of gestation, the uterus must

contract vigorously and for a prolonged period of time in order to deliver the fetus. During the later

stages of gestation, there is an increase in abundance of oxytocin receptors on uterine smooth muscle

cells, which is associated with increased "irritability" of the uterus. Oxytocin is released during labor and

it enhances contraction of uterine smooth muscle to facilitate parturition or birth.

In cases where uterine contractions are not sufficient to complete delivery, physicians and veterinarians

sometimes administer oxytocin ("pitocin") to further stimulate uterine contractions

Regulation of Oxytocin Secretion

The most important stimulus for release of hypothalamic oxytocin is initiated by physical stimulation of

the nipples or teats.

The suckling stimuli on the nipple of the breast causes signals to be transmitted through the sensory

nerves to the brain. The signals finally reach the oxytocin neurons in the PVN and SON in the

hypothalamus to cause the release of oxytocin. The oxytocin is then carried by the blood to the breasts

where it causes contraction of the myoepithelial cells that lie outside of the alveoli of the mammary

42
glands. In less than a minute after the beginning of suckling milk begins to flow. This mechanism is

called milk letdown or milk ejection.

A number of factors can inhibit oxytocin release, among them is acute stress. For example, oxytocin

neurons are repressed by catecholamines, which are released from the adrenal gland in response to many

types of stress, including fright.

Both the production of oxytocin and response to oxytocin are modulated by circulating levels of sex

steroids.

THYROID GLAND

The thyroid gland which is located immediately below the larynx on either side of and anterior to the

trachea secretes two significant hormones, thyroxine (T4 )or tetraiodothyronine and triiodothyronine

(T3) that have the effect of increasing the metabolic rate of the body. It also secretes calcitonin, an

important hormone for calcium metabolism.

Complete lack of thyroid secretion usually causes the Basal metabolic Rate (BMR) to fall about 40%

below normal, and extreme excess of thyroid secretion can cause the BMR to rise as high as 60-100%

above normal. Thyroid secretion is controlled primarily by TSH secreted in the anterior pituitary.

43
FORMATION AND SECRETION OF THE HORMONE

Synthesis of the thyroid hormones.

About 90% of the hormone secreted by thyroid gland is thyroxine and 10% is T3. However most of the

throxine is eventually converted to T3 in the tissue so that both are important functionally. These

hormones are derivatives of tyrosine and produced by the A-Cells or thyroid epithelial cells of the

thyroid gland. The thyroid hormones are stored extracellularly within the gland. The amount stored is

enough for 2-3 months even if no further synthesis were to [Link] are stored in peptide linkage

within the thyroglobulin molecule in the lumen of the thyroid follicle. The synthesis of thyroid

hormones are in two stages:

a. Synthesis of thyroglobulin.

b. Accumulation and oxidation of iodine.

Synthesis of thyroglobulin

The thyroid cells are typical protein- secreting glandular cells. The endoplasmic reticulum and

golgi apparatus synthesize and secrete into the follicles a large glycoprotein molecule called

44
 thyroglobulin with a molecular weight of 670,000. Each molecule of thyroglobulin contains 140

tyrosine amino acids and these are the major substrates that combine with iodine to form the

thyroid hormones. The T4 and T3 hormones formed from tyrosine amino acids remain a part of

the thyroglobulin molecule during synthesis of the thyroid hormones.

Iodide trapping

The first stage in the formation of thyroid hormone is transport of iodide from the ECF into the thyroid

glandular cells and follicles. The basal membrane of the thyroid cell has the specific ability to pump the

iodide actively into the interior of the cell. This is iodide trapping. In a normal gland, the iodide pump

concentrates the iodide to about 30 times its concentration in the blood. However, when the thyroid

gland becomes maximally active, the concentration ratio can rise to as high as 250 times.

Oxidation of the iodide ion

The iodide ions are oxidized to an iodine form that is capable of combining directly with the amino acid

tyrosine. The oxidation of the iodine is promoted by the enzyme peroxidase.

Iodination of tyrosin and formation of the thyroid hormone (organification of thyroglobulin).

The binding of iodine with the thyroglobulin molecule is called organification of the thyroglobulin.

Oxidized iodine even in the molecular form will bind directly but slowly with the tyrosine but in the

thyroid cells, the oxidized iodine is associated with an iodinase enzyme that causes the process to occur

within seconds or minutes.

Tyrosine is first iodized to monoiodotyrosine and then to diiodotyrosine then more and more of the

diiodotyrosine residues become coupled with each other. The product of the coupling reaction is the

molecule of thyroxin(or T4) that also remains part of the thyroglobulin molecule, or one molecule of

monoidotyrosine couples with one molecule of diodotyrosin to form triodothyronin.

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Release of thyroid hormones

The thyroxine and T3 are first cleared from the Thyroglobulin molecule and then these free hormones are

released. Over 90% of the thyroid hormones released from the gland is normally thyroxin, and slightly

less than 10% is T3 .

However, during the ensueing few days as these hormones come in contact with their target tissue most

of the thyroxine is slowly deiodinated to form additional triiodothyronin. Therefore, the hormone finally

delivered to and used by the tissues is mainly T3. A total of about 35 µg of T3 is released per day.

Transport and Concentration

When released more than 99% is bound to plasma protein as protein-bound iodine PBI, an index of

circulating level of thyroid hormones. There are 3 types of PBI

- thyroxine-binding globulin PBI(this binds 60-85%).

- Thyroxine binding pre-albumin(this binds 15-30%).

- Albumin (5-10%)bound

T3 is much less bound than T4 and there is equilibrium between bound and unbound hormone. The free

T3 diffuses more than T4 and the bound hormones are confined to the blood spaces. This means that a

larger fraction of T3 than T4 is to be found in the extracellular spaces of the body. In addition, T3 is the

active form of thyroid hormones. It has short latent period and it is about 3-4 times more potent than T4.

Physiologic functions of the thyroid hormones

All cells in the body are targets for thyroid hormones. While not strictly necessary for life, thyroid

hormones have profound effects on many physiologic processes, such as development, growth and

46
metabolism, and deficiency in thyroid hormones is not compatible with normal health. Additionally,

many of the effects of thyroid hormone have been delineated by study of deficiency and excess states.

In general they have no specific target organ and their actions are very diffuse. Most effects are

secondary to the stimulation of oxygen consumption or calorigenic effect.

1 Metabolism: Thyroid hormones stimulate diverse metabolic activities in most tissues, leading to

an increase in basal metabolic rate. One consequence of this activity is to increase body heat

production, which seems to result, at least in part, from increased oxygen consumption and rates

of ATP hydrolysis.

The thyroid hormones increase the metabolic activity of all or almost all tissues of the body. The BMR

can increase to as much as 60-100% above normal when large quantities of hormones are secreted. The

rate of utilization of foods for energy is greatly accelerated. Mental processes are excited and the

activity of most of the endocrine gland is increased.

A few examples of specific metabolic effects of thyroid hormones include:

Carbohydrate metabolism: Thyroid hormones stimulate almost all aspects of carbohydrate metabolism,

including.

i. Rapid uptake of glucose by the cells.

ii. Enhanced glycogenolysis

iii. Enhanced gluconeogenesis

iv. Increased rate of GIT reabsorption

v. Increased insulin secretion

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Effect on fat metabolism.

Increased thyroid hormone levels stimulate fat mobilization, leading to increased concentrations of fatty

acids in plasma. They also enhance oxidation of fatty acids in many tissues. Finally, plasma

concentrations of cholesterol and triglycerides are inversely correlated with thyroid hormone levels - one

diagnostic indication of hypothyroidism is increased blood cholesterol concentration.

2. Effect on Growth and maturation

It is necessary for normal growth and particularly skeletal maturation. Its growth promoting effect is

independent of that of GH. It can however potentiate the effect of GH on tissues. A classical

experiment in endocrinology was the demonstration that tadpoles deprived of thyroid hormone failed to

undergo metamorphosis into frogs. Of critical importance in mammals is the fact that normal levels of

thyroid hormone are essential to the development of the fetal and neonatal brain.

3. Temperature regulation

The thyroid hormones are important for thermoregulation and this is related to its calorigenic effect. In

hypothyroid subjects there is reduced tolerance to cold, the thyroid hormones are very important in

cold adaptation.

4 Cardiovascular system: Thyroid hormones increases heart rate, cardiac contractility

and cardiac output. They also promote vasodilation, which leads to enhanced blood

flow to many organs.

5. Central nervous system: Both decreased and increased concentrations of thyroid hormones lead to

alterations in mental state. Too little thyroid hormone, and the individual tends to feel mentally

sluggish, while too much induces anxiety and nervousness.

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6. Reproductive system: Normal reproductive behavior and physiology is dependent on having

essentially normal levels of thyroid hormone. Hypothyroidism in particular is commonly associated

with infertility.

Regulation of thyroid hormone secretion

The normal stimuli for the release of thyroid hormones via the hypothalamus are cold, stress and

fasting, while heat decreases it. Exposure of rats for several weeks to very severe cold increases the

output of thyroid hormones and BMR. Various emotional reactions can also affect the output of TRH

and TSH and can therefore indirectly affect the secretion of TH.

Feedback regulation of thyroid secretion.

Increased thyroid hormones in the body fluid decreases the secretion of TSH by the anterior Pituitary.

When the rate of thyroid hormones secretion rises to about 1.75 times normal, the rate of TSH secretion

falls essentially to zero. It has been suggested that increased thyroid hormones inhibits ant. Pit.

secretion of TSH mainly by a direct effect on the ant. Pituitary itself, though perhaps secondarily by

much weaker effects acting through the hypothalamus to inhibit hypothalamic secretion of TRH.

Abnormalities of thyroid hormones

1. Hyperthyroidism

In most patients with hyperthyroidism,the entire thyroid gland is increased to 2-3 times normal

size, with tremendous hyperplasia and folding of the follicular cell lining into the follicles so that

the number of cells is increased several more times than the size of the gland. An enlargement

of the thyroid gland is called goiter. In hyperthyroidism, there is excess secretion of the thyroid

hormones. The most common clinical case is referred to as thyrotoxicosis (Grave’s disease).

There may be a bulging of the eyes (exophthalmos). A major degree of exophthalmos occurs in

about 1/3rd of hyperthyroid patients, and the condition sometimes become severe enough that

49
 the eyeball protrusion stretches the optic nerve enough to damage vision. Much more often the

eyes are damaged because the eyelids do not close completely when the person blinks or is

asleep. As a results, the epithelial surfaces of the eyes become dry and irritated and often

infected resulting in ulceration of the cornea.

2. Hypothyroidism

Hypothyroidism is any condition that results in thyroid hormone deficiency. Two well-known

examples include:

Iodine deficiency: Iodide is absolutely necessary for production of thyroid hormones; without

adequate iodine intake, thyroid hormones cannot be synthesized. Historically, this problem was

seen particularly in areas with iodine-deficient soils, and frank iodine deficiency has been

virtually eliminated by iodine supplementation of salt.

Primary thyroid disease: Inflammatory diseases of the thyroid that destroy parts of the gland

are clearly an important cause of hypothyroidism.

In hypothyroidism there is little T3 and T4 in circulation with or without an enlargement of the thyroid

gland. It may also result in an impairment of TSH secretion.

The symptoms vary with the age of the subject. In children, there is stunted growth resulting in cretinism

while in adults puffiness of the face and eyeballs occur and it is called myxoedema.

Cretinism

It is the condition caused by extreme hypothyroidism during fetal life, infancy and childhood. It is

characterized especially by failure of growth, and mental retardation it results from congenital lack of

50
thyroid gland (congenital cretinism), from failure of the thyroid gland to produce thyroid hormones

because of genetic defect of the gland or from iodine lack in the diet (endemic cretinism).

Treatment of cretinism at any time usually causes normal return of physical growth but unless the cretin

is treated within a few weeks after birth its mental growth will be permanently retarded.

Skeletal growth in the cretin is characteristically inhibited than its soft tissue growth. As a result of this

disproportionate rate of growth, the soft tissues are likely to enlarge excessively giving the cretin the

appearance of an obese and stocky short child.

Myxoedema

Hypothyroidism during adult years producess myxoedema. A hallmark of this disorder is an edema that

causes facial tissues to swell and look puffy like the cretin. The person with myxoedema suffers from

slow heart rate, low body temperature, muscular weakness, general lethargy and a tendency to gain

weight. Because the brain has already reached maturity, the person with myxoedema does not

experience mental retardation. However in moderately severe cases, nerve reactivity may be dulled so

that the person lacks mental alertness.

ADRENAL MEDULLA

The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded

by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of cells that

secrete epinephrine (adrenaline), norepinephrine (noradrenaline), and a small amount of dopamine in

response to stimulation by sympathetic preganglionic neurons.

The adrenal medulla is functionally and embryologically a part of the sympathetic nervous system.

Rather than releasing a neurotransmitter, the cells of the adrenal medulla secrete hormones called

catecholamines. It is composed at birth of primitive sympathetic nerve cells which fully differentiate

51
into large ovoid and columnar cells called chromaffin cells (pheochromocytes) during the first 3 years of

life. In early fetal life, the medulla and other chromaffin tissues contain only nor adrenaline. The

proportion of adrenaline increases steadily after birth so that in adult man, 80% of the stored

catecholamines in the adrenal medulla is adrenaline. This is probably related to the functional

maturation of the adrenal cortex since glucocorticoids are known to be necessary for the induction of

the enzyme which converts nor adrenaline to adrenaline.

The major secretion of the adrenal medulla in man are epinephrine(80%) and nor epinephrine (20%).

There seem to be histological evidence and local stimulation of the hypothalamus that there are

adrenalin and nor adrenaline containing cells.

Formation and secretion of catecholamines

Synthesis of cathecholamines

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The catecholamines are synthesized from the amino acid tyrosine which may come from dietary sources

or from the hydroxylation of phenylalanine in the liver. The tyrosine is then hydroxylated in a rate

limting step by tyrosine hydroxylase present in the mitochondria to DOPA. Further enzymatic reaction

converts DOPA to dopamine, nor adrenaline and finally adrenaline. Catecholamines have a very short

half life, and they are metabolized in the liver. They can also be metabolized by their uptake into

neuronal tissues and also into smooth muscles and non neuronal tissues.

Once catecholamines are released, they are transported into synaptic vesicles for later release.

Catecholaminergic neurons use vesicular monoamine transporter (VMAT) to transport

Neurotransmitter molecules from the cytoplasm of the cell to the interior of the synaptic vesicles.

Vesicular packaging is important because it provides a means for releasing a predetermined amount of

neurotransmitter and it protects the neurotransmitter from degradation by enzymes within the nerve

terminal.

Regulation of secretion of catecholamines

The level of catecholamine within the nerve terminal e.g high level of cathecholamine within the

nerve terminal tend to inhibit tyrosine hydroxylase serving as a negative feedback mechanism.

The rate of cell firing: when neurons are activated and firing at a high rate, such as during stress,

tyrosin hydroxylase will be stimulated.

These mechanisms enable dopaminergic and noradrenergic neurons to carefully control their

neurotransmitter formations.

Other Common stimuli for secretion of adrenomedullary hormones include exercise, hypoglycemia,

hemorrhage and emotional distress.

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PHYSIOLOGIC EFFECTS OF CATECHOLAMINES

The physiologic effects of epinephrine and norepinephrine are initiated by their binding to adrenergic

receptors (α and β receptors) on the surface of target cells.

In general, circulating epinephrine and norepinephrine released from the adrenal medulla have the same

effects on target organs as direct stimulation by sympathetic nerves, although their effect is longer

lasting. Additionally, of course, circulating hormones can cause effects in cells and tissues that are not

directly innervated. The physiologic consequences of medullary catecholamine release are responses

which aid in dealing with stress. Generally, nor adrenaline acts preferentially on α – receptors and

causes a contraction of smooth muscles and reduces cAMP concentration while adrenaline acts on both

the α and β – receptors and generally causes relaxation of smooth muscles or metabolic effects and

increases cAMP concentration. cAMP is the intracellular mediator of catecholamine action.

The specific action of catecholamines are:

Increased metabolic rate: oxygen consumption and heat production increase throughout the body

in response to epinephrine. Medullary hormones also promote breakdown of glycogen

(glucogenolysis) in skeletal muscle to provide glucose for energy production.. Thus they have an

anti insulin effect and indeed have been shown to directly inhibit insulin release.

Stimulation of lipolysis in fat cells: this provides fatty acids for energy production in many tissues

and aids in conservation of dwindling reserves of blood glucose.

Increased rate and force of contraction of the heart muscle: this is predominantly an effect of

epinephrine acting through beta receptors.

Increased force of contraction on the skeletal muscles. They increase the force of contraction as

well as the blood flow.

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Constriction of blood vessels: norepinephrine, in particular, causes widespread vasoconstriction,

resulting in increased resistance and hence arterial blood pressure.

Dilation of bronchioles: assists in pulmonary ventilation.

Dilation of the pupils: particularly important under conditions of low ambient light.

Inhibition of certain "non-essential" processes: an example is inhibition of gastrointestinal

secretion and motor activity.

All these actions prepare the animal for the three Fs : fright, fight and flight which is known as

sympathetic discharge.

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