Chapter 10

Endocrine System
Endocrinology is the branch of biology and medicine that studies normal production andfunctions of hormones and their
disturbances. The endocrine system is a collection of glands which secretes hormones. The name "endocrine rerers to the
Tact that these glands do not have ducts that lead to the outside of the body. rather they secrete their produCtS airectly into
secreted to the blood
tne extracellular fluid. Hormone is a molecule that is produced bv an endocrine gland (e.g., thyroid),
Circulation and transported to other parts of the body. and recognized there by a specific receptor proteln. Ine association
is the biological action oT the hormone.
Or hormone with receptor induces in the target organ afunctional change, which
These actions maintain the normal functional balance of the organism, i.e, homeostasIs.
1. ENDOCRINE HORMONES
The endocrine system comprises the following
major glands: the endocrine pancreas, parathyroid -Pineal gland
glands, pituitary gland (associated with Hypothalamus Posterior pituitary
hypothalamic nuclei), thyroid gland, adrenal
glands, and gonads (testes or ovaries) (Figure 1). Anterior pituitary
These endocrine glands synthesize and secrete
bioactive hormones. Except for the gonads, which
also perform gametogenic functions, these glands Parathyroid Thyroid
are dedicated solely to hormone production (Table
1). Additionally, the placenta, a transitory organ,
performs significant endocrine functions during Skin
pregnancy. Thymus
circulation of
The secretion, diffusion, and
hormones are relatively slower than the Heart
Stomach
transmission of nerve impulses, making Liver
actions
hormones unsuitable for regulating quick Adrenal cortex
hormones are
like child fighting behavior. Instead,
long-term developmental Pancreas
essential for organizing
or physiological processes. Adrenal medulla
Small intestine
endocrine glands, there
In addition to dedicated primarily
organs
are endocrine cells within
functions (Table 1).
performing non-endocrine atrial
that produce
These include heart cells
that produce
natriuretic peptide, liver cells
(1GF-I), kidney
insulin-like growth factor type I
erythropoietin, and various
cells that produce produce
that
cells within the gastrointestinal tracthypothalamus
gastrointestinal hormones. The
or nuclei,
also contains collections of cell bodies,
neurohormones into capillaries
that secrete Figure 1: Glands of endocrine system
associated with the pituitary gland.
A third component of the endocrine system
includes numerous cell types that express highly active
inactive precursors or less active hormones into
jntfacellular, ectoenzymes, or secreted enzymes modifyingangiotensin Il Trom the inactive polypeptide angiotensinogen
generation of
hormones (Table 1). Examples include the in the liver and kidney to
and the activation of vitamin D by tWo hydroxylation reactions
tnrough two proteolytic cleavages
produce the bioactive hormone 1,25-dihydroxyvitamin D(vitamin D).
 Endocrine System 265

1:Endocrine gland and hormones

Table secreted by them
Chemical
Gland
Hormone nature

h o r m m o n e s

Synthesized and Secreted by Dedicated Endocrine Glands Protein

Pituitarygland
Growth'hormone (GH), Prolactin Peptide

Adrenocorticotropic hormone (ACTH) Peptíde

ar Solke Thyroid-stimulatinghormone (TSH) Protein

Follicle-stimulating hormone (FSH) Protein

Luteinizing hormone (LH) Protein

Amine

Thyroid gland Tetraiodothyronine (T4; thyroxine),

Triiodothyronine (T3) Peptide

Calcitonin Peptide
Parathyroid glands Parathyroid hormone (PTH) Protein

Dancreas- Islets of Langerhans Insulin, Giucagon, Somatostatin Catecholamine

Steroid
Adrenal gland Epinephrine, Norepinephrine sulfate (DHEAS)
Dehydroepiandrosterone
Cortisol, Aldosterone, Steroid
Protein
Dvaries
Estradiol-17B, Progesterone
Inhibin Steroid
Protein
Testes Testosterone
Antimüllerian hormone (AMH), Inhibin
Primary Function Other Than Endocrine Peptide
Hormones Synthesized in Organswitha
Antidiuretic hormone (ADH; vasopressin) Peptide
Brain (hypothalamus)
Corticotropin-releasing hormone(CRH) Peptide
Oxytocin,
Thyrotropin-releasing hormone (TRH) Peptide
-releasinghormone (GrnRH) Peptide
Gonadotropin re hormone (GHRH),
Somatostatin
Growth hormone releasing Amine
Amine
Dopamine
Melatonin Peptide
Brain (pineal gland) (ANP)
Atrial natriuretic peptide Protein
Heart Erythropoietin Protein

Kidney Leptin, Adiponectin Protein

Adipose tissue Gastrin, Somatostatin, Ghrelin, Protein

Stomach Secretin, Cholecystokinin Protein

Intestines
Glucagon-like peptide-1 (GLP-1) Protein
Glucagon-like peptide-2(GLP-2) Protein
Glucose-dependent insulinotropic
peptide (GIP), Motilin
Protein
Insulin-like growth factor typel (IGE-)
Conversion
Peripheral Protein
Liver
a Significant Degree by
Hormones Produced
to Angiotensin Il Steroid
1,25-Dihydroxyvitamin D (vitamin D) Steroid
Lungs
Estradiol-17B Steroid
Kidney
Adipose, mammary glands Testosterone Steroid
organs 5-Dihydrotestosterone (DHT)
gland, other
Liver, sebaceous organs
prostate, other
Genital skin,

organ regulates another

Feedback Mechanisms
where the hormone from one
cascade-like chains,
operate in produced at a distal level
systems
by feedback mechanisms, where the hormone
among endocrine glands
regulatory
balanced
is predominant mode of feedback
hormonal
Many level. This system proximal level. The
h o r m o n e s ati the
organ at a lower of
production

influences the target organs. The

circulating levels of "component B'" in
A" induces a change in
IS negative feedback.
and keeping physiological
of hormone A, maintaining stability
"hormone
loop,
feedback
inhibits the secretion
In a negative B then normal range.
in
component
glucose, within
a
change such as blood
parameters,

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 266 Animal Physiology

For example, in the hypothalamic-pituitary-gonadal axis. hypothalamic gonadotropin-releasing hormone (GnRH) stimulates
the anteior pituitary to produce follicle-stimulating hormóne (FSH) and lutelntzlng hormohe (LM), which in turn stlmulate
sex hormone production in the ovaries and testes. Increased levels of gonacdal sex hormones Inhiblt hyYpothalamle GnAH
secretion, maintaining balance in the regulatory circuit.
Positive feedback loops also exist in endocrine regulation, where hormone XIncreases levels of componernt Y, and
component Yfurtherstimulates hormone Xsecretion, This creates Instabilty and is typlcally Involved In processes like folele
rupture or childbirth. For instance, in childbirth, increased pressure on the cervlx stimulates oxytocln release, whlch
increases uterine contractions and further pressure on the cervix,escalating untl the baby is born.
There are two basic configurations of negative feedback loops within the endocrine systern: physiological response drlven
feedback loops and endocrine axis-driven feedback loops (Figure 2). In the response-drlven feedback loop,secretlon of a
hormone is stimulated or inhibited by changes in specific extracellular parameters. For example, an Increase in blood glucose
stimulates insulin secretion from pancreatic islets. The altered hormone levels change the physlology of target organs, such
as decreasing hepatic gluconeogenesis and increasing glucose uptake by muscle,whlch regulates the parameter in question.
As blood glucose levels decrease, insulin secretion is inhibited, malntaining glucose homeostasls.
In the endocrine axis-driven feedback loop, hormones produced at one level of the axis regulate the secretion of hormones
at another level,ensuring the entire axis remains in balance. An example is the hypothalamic-pltultary-thyroid axis, where
thyroid
(TSH),
hormone levels regulate the secretion of thyrotropin-releasing hormone (TRH) and thyrold-stimulating hormone
maintaining thyroid function within a normal range.

Piysioiogical Response Driven Negative Feedback Endocrine Axis Drlven Negatlve Feedback

Endocrine gland Negative feedback Hypthalmic Neuroendocrine Neurons

|Releasing Hormone
Hormone Circulating components [Target Organ)
(eg. biood glucose) Negative
Target organs
Pituatory gland}eedback -Hormone
Physiological effect
Tropic Hormone) Perlpheral
Endocrine glands

Figure 2: Physiological response-driven and endocrine axis-driven negative-feedback loops.

Much of the endocrine system is organized into endocrine axes, each consisting of the hypothalamus, pituitary gland, and
peripheral endocrine glands (Figure 2). These axes operate in a three-tiered feedback loop. The first tier involves
hypothalamic neuroendocrine neurons secreting releasing hormones. These hormones stimulate or inhibit the pituitary
gland (second tier) to produce tropic hormones. Tropic hormones then stimulate peripheral endocrine glands (third tier) to
secrete hormones like thyroid hormone, cortisol, sex steroids, and IGF-1. These peripherally produced hormones provide
feedback inhibition to both the pituitary and hypothalamus, regulating hormone levels.

An important feature of endocrine axes is the modulation of hypothalamic releasing hormones by neuronal signals. The
suprachiasmatic nucleus (SCN) in the hypothalamus imposes a circadian rhythm on these hormones and the endocrine axes
they control. Stress, whether systemic (e.g, hemorrhage, inflammation) or processive (e.g., fear, anxiety), also affects
hormone release. Major stress overrides circadian rhythms, leading to persistent hormone release that mobilzes fuels like
glucose and fatty acids while suppressing growth and reproduction. Addititonaly, cytokines from inflammatory or inmmune
responses directly regulate the release of hypothalamic and pituitary hormones.
Chemical nature of hormones
Hormones belong structurally to several categories (Table 1). They are either peptides (short chains of amino acids).
proteins (long chains of amino acids), steroids (derivatives of cholesterol), fatty acid derivatives (eicosanoids), or derivatives
of single amino acids (e.g., thyroxine), catecholamines, iodothyronines. The chemical nature of a hormone determines (1)
howitis svnthesized, stored, and released; (2) how it is transported in blood; (3) ts biological half-life and mode of clearance;
of action.
and (4) its cellular mechanism

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 enTi homan ain s tram th prima nint

naNNNtNN
ñTNinS a ONling
Amines Thñroic hormones which are
ANNVVN
homoEs aT SN•riysb in S
of thegcoprotein thyrogobulin ThyrTic NN O N i N R S
hormonebìnding iabuln (T) The ha
bnging proteins primarily thyroic mO N SA N 0 A Ý AN N
riipdhronine T3 = 18 hours). Like steroc hormones thvro
transor1ption factors
Nomone Recetors
Hormone Response Pathways Invohving Intracellular
N YM N
an horOns tha Sin
itraneliar hormone receptors are iocatec KSIe the cal iNinN N
cholestero, ad thyro hamns whh ntaÌn
membrane Steroid hormones, oertved trom N
lpi biizyer ot the memrane
Tines are ipid-solubie and can reaðily omuse through the W i
transortin tats
3a These intraceluiar hormone reCeptors act as ligand-acthated
en anuar nt
dimerize and bind to reguiztory regions of their target genes atering gene
bin t e r N Y Y
Steroid and throId hormoné binding IOCations difter slghty Stero homnes an N e s W A N N N N
that
he nuceus. in ether iocation, thiS inaing torms a hormone rereta omoe
thyroIC hormones bind to reetors a ratah N N
a snerifc segment of DNA in Contrest
hnes the binding of the hormone receptor compiex to DNA triggers transOrton ot a tang wM
ribosomes
to the cotoso and directS protein SynthesS by
t h a N NN
Steroid hormones directly initiate protein production within target cells They dise
their receotors in the cytosol, and form a receptor-hormone compiex Ths compler antey the nwhs Sins tat
Ree nthe DNA, and initiates transcription of the gene, creating messenger Athat s transiat iNtO h e N
within the cytopiasm.

Hormone Response Pathways Invotving Cell Membrane Receptors

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 268 AnimalPhysiology
Hyaropnilic, or water-soluble, hormones are unable to diffuse throuch the lipid bilayer of the cell membrane and must
tnererore pass on their message to a receptor located at the surface of the cell. Except for thyroid hormones, which are
lipid-soluble, allamino acid-derived hormones bind to cellmembrane receptors that are located, at least in part, on the
extracellular surface of the cell membrane. Therefore, they do not directly affect the transcription of target genes, but
instead initiate asignaling cascade that is carried out by amolecule called àsecond messenger. In this case, the hormone is
called afirst messenger. The most common receptor used for polar signals is G-protein coupled receptor and the second
Hessenger is cycliC adenosine monophosphate (CAMP), In the cAMP second messenger system, a water-soluble hormone
binds to its receptor in the cell membrane (Figure 3). This G-protein coupled receptor is associated with an intracelular
component called aGprotein, and bindingof the hormone activates the G-protein component. The activatd Gprotein in
turn activates an enzyme called adenylyl cyclase, also known as adenylate cyclase, which converts adenosine triphosphate
(ATP)to CAMP. As the second messenger, CAMP activates a type of enzyme called a protein kinase that is present in the
cytosol. Activated protein kinases initiate a phosphoylation cascade, in which multiple proteín kinases phosphorylate (add
aphosphate group to) numerous and various cellular proteins, including other enzymes and transcription factors.
ermones that use the GPCR-adenylyi Cyclase-CAMP second messenger system includes Adrenocorticotropic hormone
(ACTH), Angiotensin l (epithelial cells), Calcitonin, Catecholamines (B receptors), Corticotropin-releasing hormone (CRH),
Folicde stimulating hormone (FSH), Glucagon, Human chorionic gonadotropin (HCG), Luteinizing hormone (LH),
Paratthyroid hormone (PTH), Secretin, Somatostatin, Thyroid stimulating hormone (TSH) and Vasopressin (V2 receptor,
epithelial cells).
Not all water-soluble hormones initiate the CAMP second messenger system. One common alternative system uses calcium
Ions as a second messenger. In this system, Gproteins activate the enzyme phospholipase C(PLC), which functions similarly
toadenytyl cyclase. Once activated, PLCcleaves a membrane-bound phospholipid into twO molecules:
and inositol triphosphate (IP3). diacylglycerol (DAG)

Peptides Stimulus Transport Target cel

Production in rough Secretory Cytoplasm nucleus

endopiasmic reticulurm vesicie Exocytosis Free

Second messenger

Steroid Hormones
Immediate
response
Stimuius DNA

Production in smooth
Bound to
enddopiasmic reticuum plasma protein

Response
Figure 3: Signaling by peptides and steroid
Iike cAMP. DAG activates protein hormones
to be released from storage sites
kínases that initiate a phosphorylation
within the cytosol, such as from withincascade. At the same time. IP3 causes
the smooth endoplasmic calcium ions
ions then act as second messengers reticulum. The calcium
in two ways: they Can inriuence
can bind to calcium-binding proteins, the most common enzymatic and other cellular activities
madilate protein kinase within the cell. of which is
calmodulin. directlv, or they
Examples of
Upon binding calcium, calmodulin
hormones that use is able to
include angiotensin ll (Vascutar SmoothPhospholipase Cmediated DAG and calcium ions
as a second messenger system
(GHRH), Catecholamines (a receptors), Gonadotropin-releasing muscle), growth hormonereleasing
hormone hormone
hormone (TRH) and Vasopressin (V1 receptor, vascular smooth muscle). (GnRH), Oxytocin,
Thyrotropin releasing

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 Endocrine System 269

HYPOTHALAMUS AND PITUITARY GLAND

system. The pituitary
gland, or
centèr" of the endocrine
The hypothalamus-pituitary complex functions as the "command the base of the forebrain, weighing about 0.5 grams. It
hypophysis, is asmall yet complex endocrine structure located
at
consists of two main components: the adenohypophysis and the neurohypophysis.
glandand is composed
of three parts:
portion of the pituitary
the stalk), and the
pars
Theeadenohypophysis, or anteriorlobe, makes up the anterigt wraps aroound
thé pars tuberalis (which collectively
the,pars distalis (about 90% of the adenohypophysis), contains five cellItypesthat secrete
síx hormones,
intermedia (which regresses and isabsent in adult humans). It
known as anterior pituitary hormones. nervosa (posterior
hypothalamus. It includes the pars the
neural extension of the. which extends from
The neurohypophysis, or posterior lobe, is a superior end), and the infundibulum,
stalk, connecting
the
swelling at the
lobe), the median eminence (a funnel-shaped and pars tuberalis form the pituitary
median eminence to the pars nervosa.
The infundibulum
hypothalamus and pituitary gland. arginine vasopressin) and
oxytocin.
hormone (ADH or
releases neurohormones such
as antidiuretic nuclei (SON) and
paraventricular
The neurohypophysis cell bodies are located in the supraoptic the infundibular
These hormones are
whose
produced by neurons project their axons down
described as magnocellular, released from
of the hypothalamus. These neurons.
4). In response to signals, hormones are
nuclei (PVN)
to the pars nervosa (Figure called pituicytes and
( h y p o - t h a l a m o - h y p o p h y s i a l tracts)
also contains supportive glial-like cells
stalk bloodstream. The
neurohypophysis bloodstream.
diffusion into the
the axon terminals into the fenestrated capillaries, facilitating hormone
positive
isextensively vascularized with are controlled by negative and
gland are regulated by the hypothalamus and
functions of the pituitary
All endocrine
feedback loops.

Magnocellular neurosecretory cells

AON ralease

Hypothalamus
Teiease

Infundibulum

Hypothalamohypophyseal
tract
Posterior
pituitary
Pituitary
Anterior pituitary gland

Capilary plexus ADH elease

hypothalamus release oxytocin (OT) or ADH into

the posterior lobe of the pituitary
Figure 4: Neurosecretory cells in the
the blood via the capillary plexus.
gland. These hormones are stored or released into

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270 Animal Physiology

Synthesis of ADH and Oxytocin

ADH and oxytocin are nonapeptides, each consisting of uine amino acids,and differ in only two amino acids, resulting in
limitedovelapping activity. Both homones are synthesized as pre-prohormones in the hypothalamic magnocelular cell
bodies and are packaged into neurosecretory granules (Figure 5).

Exon Intron Exon Intron Exon

2

Gene Signal Homone NP Neurophysin (NP) NP Glycopaptide

Transcription,
excision, splicing

Messanger RNA Signai Hormone Neurophysin Giycopeptide

Transiation
Processing
Packaging

Protein products Glycopepide

Hormore

Figure 5: Synthesis and processing of pre-pro-vasopressin or pre-pro-oxytocin.

Each prohormone for ADH and oxytocin includes the hormone itself and a co-secreted peptide: neurophysin I (with ADH)
or neurophysin Il (with oxytocin). These preprohormones are known as preprovasophysin and preprooxyphysin,
respectively. Upon entering the endoplasmic reticulum, the N-signal peptide is cleaved of. The prohormone is then
packaged within the endoplasmic reticulum and Golgi apparatus into membrane-bound secretory granules within the
supraoptic and paraventricular nuclei. ADHis primarily formed in the supraoptic nuclei, while oxytocin is primarily formed
in the paraventricular nuclei. The secretory granules are transported intra-axonally down the infundibular stalk to the axonal
termini in the pars nervosa via an ATP-dependent transport mechanism. During this transport, pro-vasopressin is
proteolyticaly cleaved into the active hormone (AVP/ADH), neurophysin (NP), andaC-terminal glycoprotein (GP),. NP forms
tetramers that bind five AVP molecules. All three fragments are released from the axonal termini in the pars nervosa
(posterior pituitary) into the systemic circulation, with only AVP (ADH) being biologically active (Figure 6). Axonal swellings
due to stored secretory granules, visible under light microscopy, are termd Herring bodies.

slici
PrusasLSR

CryomosnE

AVP-NH

Fndeglasmic
ptutary tak

compi Nssosecrelory Axon temsa!

9ranule irs posleriOr
piusry

Figure 6: Synthesis, processing, and transport ofip pre-pro-vasopressin.

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 Endocrine System 271

dendrites
resnonse tostimuli detected primarily at the cell bodies and
ADH and OXytocin are released from the parsnervosa in hypothalamus. These stimuli are mainly neurotransmtles
in the supraoptic (SON)and paraventricular nuclej (PVN)othe all av
stimulatión occurs, neurons depolar1ze and propagale stimulus
released trom hypothalamic intermeurons, When sufficient triggering a
action notential increases intracellular (Ca"], extracellular Tiuid OT
potential down the axon. At the axonal ternini. this into the
of ADH or oxvtocin. along with neurophysins,
secrenon response that results in the exOCvtosis neurophysinsthen enter the peripheral circulation and can be measured in tne
hormones and
the pars hervosa (Figure 6). The
blood.
Structuralsimilarity in Antidiuretic Hormone and Oxytocin amino acid
polvpeptides, each containing nine amino acids. Their
(Arginine vasopressin-AVP) are
Botn oxytocin and ADH
sequences are the following:
-GlyNH2
Vasopressin: Cys-Tyr- Phe-Gln-Asn-Cys-Pro- Arg
-GlyNH2
Oxytocin: ys-Tyr- Ile -Gln-Asn-Cys-Pro- Leu replace isoleucine
vasopressin, phenylalanine and arginine
that in
are almost identical except
Note that these two hormones
and leucine at3rd and 8th position of the oxytocin molecule.
Hormone (ADH)
Physiological Effect of Antidiuretic preventing dehydration.
When
kidneys to retain water (antidiuresis), signal
hormone, primarily acts on
the osmoreceptors
ADH, or antidiuretic vomiting, a salty meal, or prolonged standing, to water and
to dehydration,exercise,
permeability
kidneys, increasing their
blood osmolarity is high due targets tubular cells in the excreted in the urine,
the posterior pituitary
to release ADH, ADH
water being returned to
the blood and less being
results in more
enhancing water reabsorption,This
constricts
thus lowering blood osmolarity. concentrations, ADH also
by the kidneys. At higher
conservation ADH release
concentrations, ADH
promotes water
which is why it is also known as vasopressin.
At low pressure, sense the change
body, increasing arterial osmolarity decreases, hypothalamicosmoreceptors
arterioles throughout the
feedback loop. When blood
controlled by anegative water reabsorption.
secretion, leading to less dehydration, and
and reduce ADH causing increased urine production,
secretion. Alcohol inhibits
ADH release,
chronic underproduction
of ADH, leads to chronic
Drugs can affect ADH condition characterized by their kidneys do not
Diabetes insipidus, a but without sufficient ADH,
potentially ahangover. and drink more fluids,
this condition feel thirsty electrolyte imbalances.
dehydration. Patients with solute concentrations and potential
high blood
leading to persistent
reabsorb enough water,

Physiologicaleffects of
oxytocin contractions and cervical
hormone oxytocin stimulates uterine
complete, the
peptide-derived
uterus. However, towards
the end of
When fetal development is receptors are not highly expressed in the oxytocin. Oxytocin is
pregnancy, oxytocin to
dilation. During most of uterine smooth muscle cells more sensitive
increases, making the
pregnancy, their synthesis feedback mechanism.
during childbirth through a positive the
released continuously
stretches the cervix and triggers
push the fetal head towards the cervix, which contractions and
Oxvtocin-induced uterine contractions This increases the intensity of
oxytocin from the pituitary.
hypothalamus to produce and release more birth.
continuing the feedback loop until
further ilates the cervix, maternal and newborn health. It is
decrease, but oxytocin remains important for
After birth, the mother's oxytocin levels newborn suckles, sensory receptors
in breastfeeding women. When the
essential for the milk ejection reflex, or "let-down," bloodstream. This causes cells
hypothalamus, prompting the release of oxytocin into the
in the nipples send signals tothe
milk into the infant'smouth.
inthe milk ducts to contract,ejecting attachment, and is involved in
feelings of love,
plays a role in parent-newborn bonding, known as
Additionally, oxytocin
closeness, and the sexual response in
both males and females.

The Adenohypophysis
Because of the histological
endocrine celi types that produce six hormones (Table 2).
The pars distalis is composed of five referred to as pituitary basophils,
corticotropes, thyrÍtropes, and gonadotropes are
characteristics of the cell types, the
açidophil.
lactotropes are referred to as pituitary
whereas the somatotropes and

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Each endocrine axis of the adenohypophysis (anterior

Hypothalamus
pituitary) involves three levels of endocrine cells { XRH
(Figure 7):
XIH
1. Hypothalamic neurons: These neurons release
specific hypothalamic releasing hormones (XRHS)
that stimulate the secretion of specific pituitary XRH
tropic hormones (XTHs). In some cases, the Short
production of pituitary tropic hormones is loop
regulated by release-inhibiting hormones (XIHs).
2. Anterior pituitary cells: These cells secrete tropic XTH
hormones (XTHs) that act on specific peripheral Pituatory Long
target endocrine glands. loop
3. Peripheral endocrine glands: These glands release
peripheral hormones (X) in response to the tropic
hormones. The peripheral hormone regulates
various physiological functions and provides Peripheral Gland
negative feedback to the pituitary gland and
hypothalamus, inhibiting the production and
secretion of tropic and releasing hormones, Figure 7: Negative-feedback loops regulating hormone secretion
respectively. in atypical hypothalamus-pituitary-peripheral gland axis.
The hypothalamic level of regulation is neurohormonal. Collections of neuronal cell bodies, called nucei, are located in
several regions of the hypothalamus, collectively referred to as the hypophysiotropic region. These nuclei are distinct from
the magnocellular neurons of the PVN and SON that project to the pars nervosa. They have small, or parvicellular, neuronal
cell bodies that project axons to the median
eminence. Parvicellular neurons secrete
releasing hypophysiotropic hormones from
their axonal termini at the median
eminence (Figure 8). These releasing
hormones enter a primary plexus of
fenestrated capillaries and are conveyed to
a second capillary plexus in the pars distalis
Parvoceliular
by hypothalamohypophysial portal neurosécretory
vessels. At the secondary capillary plexus, celis
the releasing hormones diffuse out of the
vasculature and bind to their specific Hypothalamus Hormone transport
in axons

receptors on cells within the pars distalis. Median eminence

The neurovascular link (pituitary stalk) Hypophysiotropic
between the hypothalamus and pituitary is hormones released
delicate and can be disrupted by trauma, Capillary beds
surgery, or hypothalamic disease, leading to Hormone transport
a decline in all anterior pituitary tropic Hypothalamohypophyseal in blood
portalveBsels
hormones except prolactin. The cells of the Stimulation or inhibition
adenohypophysis represent the Anterior lobe of anterior pituitary
intermediate level of an endocrine axis. The of pituitary hormone release
adenohypophysis secretes protein
Hormone transport
hormones known as tropic hormones: Hormone in blood
Secreting cells
ACTH,TSH, FSH, LH, GH, and PRL (Table 2).
Tropic hormones bind to their receptorson Action on endocrine
peripheral endocrine glands, generally not glande
directly regulating physiological responses
Figure 8: Neurovascular link
but instead influencing peripheral hormone between the
production.
lobe (pars distalis) of the pituitary. hypothalamus and the anterior
 Endocrine System 273

Hypothalamic Regulation, and Feedback

Tabie Z: CellTypes of the Adenohypophysis: Hormonal Production and Action,
Regulation
Acidophils
Basophils
Sormatotrope Lactotrope
Corticotrope Thyrotrope Gonadotrope Dopamine
decapeptide, GHRH: 44-aa
Primary CRH: TRH: GnRH: (catecholamine):in
peptide,
hypothalamic 41-amino acid tripeptide, stimulatory hibitory
stimulatory
regulation peptide, stimulatory Somatostatin: Prolactin-releasíng
stimulatory 14 aa-peptide, factor: stimulatory
inhibitory
22-kDa Prolactin: 23-kDa
FSH, LH: 28- and 33-kDa GH:
Tropic ACTH: 4.5-kDa TSH: 28-kDa
glycoprotein hormones protein protein)
hormone protein glycoprotein
secreted hormone receptor
GH Jeceptor PRL
Receptor MC2R (G,-inked TSH receptor FSH and LH receptors (Gs (JAK/STAT-linked
linked GPCRs) (AK/STAT
GPCR) (G-linked linked cytokine cytokine receptor)
GPCR) receptor)
No endocrine
theca and Liver
Target Adrenal cortex : Thyroid Ovary: target organ-not
Zona fasciculata epithelium granulosa) of an
endocrine part

gland and Zona Testis Leydigand Sertoli endocrine axis

reticularis cells
GH (short None
Cortisol Triiodo Estrogen, progesterone, GF-I
Negative testosterone, and inhibin loop)
feedback by thyronine release of FSH from the
positive feedback in women and Inhibin selectively inhibits
Note: Estrogen can also have a
gonadotrope. gonadotropes,
consists of severalendocrine cell types: corticotYopes, thyrotropes,
The adenohypophysis (anterior pituitary)
somatotropes, and lactotropes (Table 2). hypothalamic-pituitary-adrenal axis. They
Corticotropes: These cells stimulate the adrenal cortex as part of the acid peptide synthesized as
1. (ACTH, also called corticotropin), a 39-amino referred to as POMC cells.
produce adrenocorticotropic hormone are also
pro-opio-melanocortin (POMC). Corticotropes
part of the larger prohormone, melanocyte-stimulating hormone (MSH), endorphins (endogenous
POMC Contains peptide sequences for ACTH, convertase that produces
(Figure 9). In humans, corticotropes express the prohormone
opioids), and enkephalins POMC, sUch as the N
sole active hormone secreted from these cells. Other fragments cleaved from
ACTH as the humans.
(-LPH), do not have a physiological role in
terminal fragment and B-lipotropic hormone stimulates the thyroid gland to
thyroid-stimulating hormone (TSH), which
2. Thyrotropes: These cells produce
produce thyroid hormones. (FSH), which
hormone (LH) and follicle-stimulating hormone
3. Gonadotropes: These cells produce luteinizing
and testes).
regulate the function of the gonads (ovaries in various
Somatotropes: These cells produce growth hormone
(GH), which stimulates growth and metabolism
4

stimulates milk production in the mammary glands.

tissues.
(PRL), which
5. Lactotropes: These cells produce prolactin
melanocortin 2 receptor
an unbound hormone with a short half-life of about 10 minutes. It binds to the
ACTH circulates as production, enhances the expression
increases cortisol and adrenal androgen
(MC2R) on adrenal cortex cells. ACTH acutely in the adrenal cortex over the long
promotes the growth and survival of two zones
of steroidogenic enzyme genes, and expresses the peptide
subset of parvicellular hypothalamic neurons
term, ACTH is regulated by the hypothalamus. A
procorticotropin-releasing hormone (pro-CRH) (Table 2).
stimulates ACTH secretion and increases
into an amidated 41-amino acid peptide, CRH, which acutely
Pro-CRH is processed
CRH-expressing neurons also co-express ADH,
which potentiates the action of CRH
transcription of the POMC gene. These morning and reaching a low in
corticotropes. ACTH secretion follows a pronounced diurnal pattern, peaking in the early
on
CRH, and consequently ACTH, ispulsatile.
the late afternoon. Additionally, the secretion of

Publications
 274 AnimalPhysiology

Signal (26) Preproopiomelan0cortin (285)

(146) B-Lipotropin (91)

N-terminal peptide (76) ACTH (39) y-Lipotropin (58) B-Endorphin (31)

$SH MSH
(13) CLIP
a MSH

Figure 9: The original gene transcript of proopiomelanocortin contains structures of multiple bioactive compounds. ACTH.
adrenocorticotropic hormone; CLIP, corticotropin-like intermediate peptide; MSH, melanocyte-stimulating hormone.
Thyrotropes
B-TSH subunit TSH TSH receptor
Thyrotropes regulate thyroid function by
secreting thyroid-stimulating hormone (TSH,
also called thyrotropin) as part of the B-FSH subunit FSH FSH receptor
Pus
hypothalamus-pituitary-thyroid axis. TSH is one a-glycoprotein
of three pituitary glycoprotein hormones, along subunit
with follicle-stimulating hormone (FSH) and B-LH subunit (o-GSU) LH
>LH receptor
luteinizing hormone (LH) (Table 2). TSH is a
heterodimer composed of an a subunit (a-GSU) B-hCG subunit hCG LH receptor
common to TSH, FSH, and LH, anda Bsubunit (B
TSH)specific to TSH (Figure 10). Glycosylation of Figure 10: Pituitary glycoprotein hormones.
these subunits enhances their stability in circulation and increases the
receptors. The half-lives of TSH, FSH, and LH range from tens affinity and specificity of the hormones for their
of minutes to several hours.
TSH binds tothe TSH receptor on thyroidepithelial cells,
stimulating all aspects of thyroid function, including hypertrophy,
hyperplasia, and survival of these cells. In regions with limited iodide
feedback, potentially causing goiter, a noticeable thyroid enlargementavailability, TSH levels elevate due to reduced negative
in the neck.
The pituitary thyrotrope is stimulated by
thyrotropin-releasing hormone (TRH) (Table 2), produced by parvicellular
hypothalamic neurons. TRH is a tripeptide synthesized as
receptor on thyrotropes, and its release follows adiurnala larger prohormone containing six TRH Copies. TRH binds to its
dinnertime. Various types of stress, including physical stresS, rhythm, peaking overnight and reaching its lowest around
starvation, and infection, inhibit TRH secretion.
The active form of thyroid hormone,
triiodothyronine
TRH-producing neurons. T3 suppresses B-TSH expression(T3), provides negative feedback on both
and reduces thyrotrope sensitivity to TRHpituitary thyrotropes and
while also inhibiting TRH
production and secretion.
The Gonadotrope
Gonadotropes secrete follicle-stimulating hormone (Fs) and
gonadotropins, in response to gonadotropin-releasing hormone (GnRH)luteinizing hormone (LH). colectively known a5
the function of gonads in both sexes. GnRH is secreted during from the hypothalamus.
infancy and from puberty These hormones regulate
active at all stages of development. During embryonic development,
GnRH
onward, although the pituitary i5
hypothalamus from the nasal placode. In Kallmann syndrome, mutations in the neurons migrate to the mediobasal
tertiary hypogonadotropic hypogonadism and anosmia (loss of ismell),
s KAL gene disrupt this migration, leading to
resulting in lower levels of circulating gonadotropints.