Introduction – CC3
MECHANISM OF HORMONAL ACTION
Course Outline
Definition of Endocrinology
Definition of Hormones
Classification of Hormones
Mechanism of Hormonal Action
Hormonal Interaction
Endocrine system
Group of ductless glands that secrete hormones
necessary for normal growth and development,
reproduction, and homeostasis
In humans, the major endocrine glands are the
hypothalamus, pituitary, pineal, thyroid,
parathyroid, adrenals, islet of Langerhanns in the
pancreas, ovaries and testes
Endocrine Action
A network of ductless glands of internal secretions
Considered to be the regulatory system of the body
Reregulated by means of control of hormone
synthesis rather than by degradation.
Hormones serve as chemical messenger in the body
to produce biochemical changes
Refers to the collection of hormones
Hormones
Each hormone is produced by a specific endocrine
gland
Chemical signals produced by specialized cells
secreted into the blood stream and carried to a target
site of action as free hormone or bound to transport
protein
They play an important role in the growth and
development of an organism
Hormones
They are regulated by the metabolic activity either
positive or negative feedback mechanism
Positive feedback mechanism – a INCREASE in the
product , causing an INCREASE in the activity of the
system and the production rate
Negative feedback mechanism – an INCREASE in the
product, causing DECREASE in the activity of the
system and the production rate
Major function: to maintain the constancy of chemical
composition of ECF and ICF
Hormones
Chemical compounds secreted into the blood that affects
tissues generally at a site distant from original production
Chemical messenger
3 characteristics of hormone
1. Each hormone is produced by specific tissue
2. Hormones are released directly from the tissue into the
bloodstream and carried to the site of action
3. Each hormone acts at a specific site or sites(target cells)to
induce certain characteristic biochemical changes
How to describe or classify hormones
1
1. Many Possible Classification Schemes --
Hormones can be classified by
effect,
chemical nature,
source
2. Look for:
(1) the major hormone-producing glands
(2) details for specific hormones
Summary of typical hormone roles and examples
1. Stress response -- cortisol, epinephrine.
Regulate heart rate, blood pressure, inflammation,
etc.
2. Maintenance of Homeostasis -- insulin,
glucagon, cortisol. Regulate blood glucose/energy
supplies and concentrations of substances in general.
Maintain more or less constant conditions =
homeostasis.
Summary of typical hormone roles and examples
3. Regulation of episodic or cyclic events --
estrogen, insulin, oxytocin -- regulate lactation,
pregnancy, effects of eating, etc.
4. Growth/overall regulation -- growth factors, tropic
hormones -- regulate production of other hormones.
(Note: not all GF's are endocrines.)
5. Hormones may have more than one function. For
example, cortisol is constantly made to maintain
homeostasis, but it is secreted in larger amounts in
response to stress.
Classification of Hormones According to Composition and Structure
1. Peptides and Proteins
Synthesized and stored within the cell in the form of secretory
granules and are cleaved as needed
They cannot across the cell membrane and thus, produce their
effects in the outer surface of the cell
Water soluble and bound to carrier protein
Examples
Glycoprotein – FSH, hCG, TSH, Erythropoetin
Polypeptides – ADH, GH, Angiotensin, Calcitonin,
Cholecystokinin, Gastrin, Glucagon, Insulin, MSH, Oxytocin,
PTH, Prolactin, Somatostatin
Classification of Hormones According to Composition and Structure
2. Steroids
Are lipid molecules that have cholesterol as a common precursor
They are produced by adrenal glands, ovaries, testes and placenta
They are water insoluble and circulate, but not bound to a protein
carrier
Aldosteron, Cortisol, Estradiol, Estrone, Progesterone, Testosterone,
Androgens
3. Amines
Derived from amino acid and they are intermediary between steroid
and protein hormones
Epinephrine, Norepinephrine, T3, T4, Serotonin
Classification of Hormones According to tissue of Origin
Tissue of Origin
Hormones produced
Hypothalamus
TRH, GnRH, CRF
Anterior Pituitary
TSH,ACTH, FSH, LH, prolactin,
growth hormon
Posterior Pituitary Vasopressin, oxytocin
Adrenal Medulla Epinephrine,norephinephrine
Adrenal Cortex Cortisol, aldosterone
Parathyroid Parathyroid hormone
Thyroid T3,T4, calcitonin
Pancreas Insulin, glucagon
Ovaries Estrogen
Testes Testosterone, other androgen
Hormone secretion can be stimulated and inhibited by:
Other hormones (stimulating- or releasing-
hormones)
Plasma concentrations of ions or nutrients, as well as
binding globulins
Neurons and mental activity
Environmental changes, e.g., of light or temperature
Hormonal Interaction
1. Synergistic
· 2 or more hormones are additive/complementary in effect
The effect of one hormone is the same as the action of the
other
Example: Thyroid Hormone + Growth Hormone
·2. Antagonistic
Hormone offsets another hormone
The effect of one hormone is against the action of another
Example: The regulation of plasma glucose involves insulin
[for increased blood glucose] and glucagon [for decreased blood
glucose] hormones
Hormonal Interaction
3. Permissive
Hormone will enhance the responsiveness of a
target to another hormone
Example: Increased thyroid hormone levels,
tissues become more responsive to catecholamine
Hormonal Interaction
4. Potentiation reaction
The presence of one hormone increase the action
of another
5. Stimulatory reaction
The presence of one hormone stimulates the
secretion of another
6. Inhibitory reaction
The presence of one hormone inhibits the
secretion of another
Types of Hormone Actions
1. Endocrine
Secreted in one location and release into blood
circulation; binds to specific receptor to elicit
physiological response
2. Paracrine
Secreted in endocrine cells and release into
interstitial space; binds into specific receptor in
adjacent cell and effects its function
Types of Hormone Actions
3. Autocrine
Secreted in endocrine cells and sometimes
release into interstitial space; binds into
specific receptor on cell of origin resulting to
self-regulation of its function
Types of Hormone Actions
4. Juxtacrine
Secreted in endocrine cells and remains in
relation to plasma membrane; acts on
immediate adjacent cell by direct cell-to-cell
contact
5. Exocrine
Secreted in endocrine cells and released
into lumen of gut; it effects their function
Types of Hormone Actions
5. Neurocrine
Secreted in neurons and released into extracellular
space; binds to receptor in nearby cell and effects its
function
6. Neuroendocrine
Ssecreted in neurons and released from nerve
endings; interacts with receptor of cells at distant site
ACTIONS OF HORMONES IN GENERAL
1. Regulatory Function
To maintain constancy of chemical composition of extracellular and
intracellular fluids
2. Morphogenesis
Some hormones play an important part in controlling the growth and
development of an organism
3. Integrative Action
Each hormone has specific function, however, hormones by several
endocrine glands may be important for regulating a single function
Hormone Concentrations
Threshold- hormone will not have any
physiological effect until hormone threshold is
reached
· Concentration effect- differential physiology
depending on concentration
· Example: Testosterone- surge of testosterone after
puberty · Growth of auxiliary/pubic/facial hair, and
muscle mass However, Injection of large amount of
testosterone can lead to even more effects such as
acne and growth of breast tissue.
Hormone Concentrations
Half-life- the time it takes for the concentration of a
hormone to reduce 50%
· Liver filters the concentration of hormones via blood.
Kidney can excrete a certain amount of hormones.
·
Endocrine has the longest half-life because it has to enter
the blood stream and travel to the target.
· Autocrine has the shortest half-life because it is secreted
into its cell of origin being targeted
· Receptor Saturation- hormone receptor are not a
set number. Can down regulate if bombarded with
hormones
Factors affecting Hormonal Secretion
1. Stimulatory and Inhibitory Agent. These
include Hypothalamic peptides or
neurotransmitters.
These may influence hormone synthesis or release.
2. Many hormones such as GnRH, are released
pulsatile fashion.
3. Some hormones exhibit a circadian rhythm. ACTH,
consequently cortisol, TSH, GH, and even parathyroid hormones
have peak secretion at different time during the day or night.
Factors affecting Hormonal Secretion
4. Stress can increase hormone synthesis and release.
Examples are ACTH, GH, and Prolactin.
5. Hormone synthesized by target organ/ cells may
feedback to the main endocrine glands.
6. Change in metabolic products as a result of hormone
action may likewise exert feedback control.
7. Other hormones or drug may modulate normal
endocrine responses.
Control of Hormone Secretion
The majority of endocrine functions are regulated
through the pituitary glands, which in turn is
controlled by:
1. secretion from the hypothalamus. The
posterior part of pituitary secretes some hormones
that have different effect on end organs
(VASOPRESSIN AND OXYTOCIN)
Control of Hormone Secretion
2. From its anterior part, it secretes a group of
stimulating hormones that circulate to other
endocrine gland and cause those glands to secrete
hormones that then directly affect end organs.
3. A tight feedback control is usually present
among all these secretions.
Hormone Binding to cell receptors
Hormone -------
Cell membrane Receptor
Hormonwe
Adenylate G-protein
cyclase
cAMP +Phosphate
ATP
Regulate
Active Protein the cell
Inactive
kinase Function
Protein kinase
AMP Phosphodiester
cAMP
Hormonal Binding to Cell membrane Receptor
1. Peptide or protein , and catecholamine cannot
pass the lipid membrane of the cell because of
either large molecular size or polarity or
molecular charge that make them insoluble
in lipid.
Hormonal Binding to Cell membrane Receptor
2. Whenever a hormone in the circulation will be
effective at a particular tissue site depends on the
presence of receptor molecules specific for
that hormone on cell surface.
3. The receptor molecule for a given hormone will
recognize no other hormones.
Hormonal Binding to Cell membrane Receptor
Steps:
1. As the hormones bids to the correct receptor in the
cell membrane, the cell is stimulated thru a
series of activation steps resulting in the
synthesis of the second messenger (that
transmits the stimulation of the signal intracellular).
Example of these second messengers: Cyclic
adenosine 3’5’ monophosphate ( cyclic AM –
c AMP), inositol phosphate, and calcium ion.
Hormonal Binding to Cell membrane Receptor
2. Some hormone receptors extend from the
extracellular side thru the cell membrane to
interact with guanine nucleotide binding
protein (G-Protein) on the cytoplasmic side of the
membrane.
Binding of hormone to receptor promotes an
association, with the G-protein, which then give up a
molecule of guanine diphosphate (GDP) and pick
up another molecule of guanine triphosphate (GTP).
Hormonal Binding to Cell membrane Receptor
3. This complex interacts with adenylate cyclase
in the cytoplasm to convert adenosine
triphosphate (ATP) to cAMP.
This second messenger cAMP diffuses thru out the
cytoplasm, where it is activated by an enzyme called
c AMP –dependent protein kinases in order to
be able to phosphorylate other proteins that control
cell processes.
Hormonal Binding to Cell membrane Receptor
4. Theintercellular concentration of cAMP is
regulated by the enzymes
phosphodiesterase which converts
into AMP.
The pituitary hormones, ACTH, FSH,
LH,and TSH, as well as human
chorionic gonadotrophin, parathyroid,
catecholamine, glucagon generated by
cAMP by this mechanism.
Hormonal Binding to Cell membrane Receptor
5. An analogous series of reaction
occurs for some other hormone
(releasing factors, ADH) in which
binding to the receptor and interaction
with a G-protein result in activation of
the enzyme phospholipase C, which
generates inositol phosphate.
Hormonal Binding to Cell membrane Receptor
This molecule causes the release of
intercellular calcium ions, which
activate protein kinase .
Through this type of reaction and also
by binding to calmodulin, calcium ion
acts has a second messenger.
Hormonal Binding to Cell membrane Receptor
Still another mechanism for
hormone action involves binding to
a receptor that stimulate tyrosine
kinase activity directly without a
second messenger.
Insulin and some growth
factors act thru this mechanism.
Hormonal Binding to Cell membrane Receptor
A complete mechanism of hormone action is
6.
employed by steroid and thyroid hormone
that are able to move across the cell
membrane.
Steroid
hormone binds to receptor
molecules in cytoplasm and are transported
to the cell nucleus, where the active complex
of hormone and recptor stimulate mRNA
transcription of specific genes.
Hormonal Binding to Cell membrane Receptor
Thyroid hormone similarly stimulates
transcription by interacting with
receptors in chromatin nucleus.