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.
 
