1. Mechanism of Hormone Action
dr. Dian Hasanah
Laboratorium Fisiologi
Fakultas Kedokteran Universitas Brawijaya
2. Chemical Messenger
The multiple activities of the cells, tissues, and organs of
the body are coordinated by the interplay of several types
of chemical messenger systems.
Several types of chemical messenger systems:
a. Neurotransmitters are released by axon terminals of
neurons into the synaptic junctions and act locally to
control nerve cell functions. Example: acetylcholine.
b. Endocrine hormones are released by glands or
specialized cells into the circulating blood and influence
the function of cells at another location in the body.
3. Chemical Messenger
c. Neuroendocrine hormones are secreted by neurons into the
circulating blood and influence the function of cells at another
location in the body. Examples: oxytocin, vasopressin.
d. Paracrines are secreted by cells into the extracellular fluid and
affect neighboring cells of a different type. Example:
somatostatin secreted by delta cells in the pancreas.
e. Autocrines are secreted by cells into the extracellular fluid and
affect the function of the same cells that produced them by
binding to cell surface receptors. Examples: somatomedin, some
growth factors.
f. Cytokines are peptides secreted by cells into the extracellular
fluid and can function as autocrines, paracrines, or endocrine
hormones. Example: interleukins.
5. Body’s Two Major Regulatory Systems
The endocrine system is one of the body‟s two major
regulatory systems. The other one is the nervous system.
In general, nervous system coordinates rapid, precise
responses and is especially important in mediating the body‟s
interaction with the external environment.
The endocrine, by contrast, primarily controls activities
that require duration rather than speed. It
regulates, coordinates, and integrates cellular and organ
function at distance.
6. The Functions of Endocrine System
1. Regulating organic metabolism and H2O and electrolyte
balance, which are important collectively in mantaining a
constant internal environment.
2. Inducing adaptive changes to help the body cope with
stressful situations.
3. Promoting smooth, sequential growth and development.
4. Controlling reproduction.
5. Regulating red blood cell production.
6. Along with the autonomic nervous system, controlling and
integrating activities of both the circulatory and digestive
systems.
7. Complexity of the Endocrine System
a. A single endocrine gland may produce multiple hormones. Example:
anterior pituitary secretes 6 different hormones (GH, FSH, LH,
prolactin, TSH, ACTH).
b. A single hormone maybe secreted by more than one endocrine gland.
Example: somatostatin is secreted by hypothalamus and pancreas.
c. Frequently, a single hormone has more than one type of target cell and
therefore can induce more than one type of effect, typically by binding
with different subtypes of receptors. Example: vasopressin binds V1a
and V2 receptors.
d. The rate of secretion of some hormones varies considerably over the
course of time in a cyclic pattern. Therefore, endocrine systems also
provide temporal (time) coordination of function. This is particularly
apparent in endocrine control of reproductive cycle. Examples:
estrogen, progesterone.
8. Complexity of the Endocrine System
e. A single target cell may be influenced by more than one hormone.
Some cells contain an array of receptors for responding in
different ways to different hormones. Example: liver cells are
influenced by insulin and glucagon.
f. The same chemical messenger may be either a hormone or a
neurotransmitter, depending on its source and mode of delivery
to the target cell. Example: norepinephrine.
g. Some organs are exclusively endocrine in function (they
specialize in hormone secretion alone), example: anterior
pituitary. Whereas others also perform nonendocrine
functions, examples: testes secrete testosterone and also
produce sperm.
9. Definition of Hormone
Hormone is a blood-borne chemical messenger
synthesized and released by endocrine gland that
act on target cells located a long distance from the
location it released.
Tropic (means “nourishing”) hormone is a hormone
that its primary function is to regulate hormone
secretion by another endocrine gland and to
maintain their endocrine target tissues.
10. Classes of Hormones
Classes of hormones based on chemical structure:
a. Proteins and polypeptides, including hormones secreted by the
anterior and posterior pituitary gland, the pancreas (insulin and
glucagon), the parathyroid gland (parathyroid hormone), and many
others.
b. Steroids secreted by the adrenal cortex (cortisol and
aldosterone), the ovaries (estrogen and progesterone), the testes
(testosterone), and the placenta (estrogen and progesterone).
c. Derivatives of the amino acid tyrosine, secreted by the thyroid
(thyroxine and triiodothyronine) and the adrenal medullae (epinephrine
and norepinephrine).
There are no known polysaccharides or nucleic acid hormones.
11. Classes of Hormones
Classes of hormones based on their solubility in water
or lipid:
a. Water-soluble hormones (hydrophilic): peptides
and catecholamines.
b. Lipid-soluble hormones (lipophilic): steroid and
thyroid hormones.
12. Hormone Receptors
The locations for the different types of hormone receptors
are generally the following:
a. In or on the surface of the cell membrane. The
membrane receptors are specific mostly for the
protein, peptide, and catecholamine hormones.
b. In the cell cytoplasm. The primary receptors for the
different steroid hormones are found mainly in the
cytoplasm.
c. In the cell nucleus. The receptors for the thyroid
hormones are found in the nucleus and are believed to be
located in direct association with one or more of the
chromosomes.
13. Plasma Concentration
Plasma concentration of a hormone is influenced by:
a. Hormone secretion.
b. Peripheral hormone conversion. Example: T4 T3 (more active).
c. Hormone transport (bound or unbound to plasma protein).
d. Hormone inactivation.
Peptide hormones are inactivated by hydrolysis of peptide
bonds; or engulfed and degradaded intracellularly.
Catecholamines are enzymatically converted into inactive
forms.
Lipophilic hormones are inactivated by alteration of the
active portions, and liver adds charged groups to make them
water soluble.
a. Hormone excretion by liver and kidneys.
14. Hormone Clearance
Hormones are “cleared” from the plasma in several
ways, including:
a. Binding with the tissues.
b. Metabolic destruction by the tissues.
c. Excretion by the liver into the bile.
d. Excretion by the kidneys into the urine.
15. Negative Feedback
After a stimulus causes release of the hormone,
conditions or products resulting from the action of
the hormone tend to suppress its further release.
In other words, the hormone (or one of its
products) has a negative feedback effect to
prevent oversecretion of the hormone or
overactivity at the target tissue.
17. Positive Feedback
In a few instances, positive feedback occurs when the
biological action of the hormone causes additional secretion
of the hormone.
One example of this is the surge of luteinizing hormone (LH)
that occurs as a result of the stimulatory effect of
estrogen on the anterior pituitary before ovulation. The
secreted LH then acts on the ovaries to stimulate additional
secretion of estrogen, which in turn causes more secretion
of LH.
18. Neuroendocrine Reflexes
Many endocrine control systems involve neuroendocrine
reflexes, which include neural as well as hormonal
components.
The purpose of such reflexes is to produce a sudden
increase in hormone secretion in response to a specific
stimulus, frequently a stimulus external to the body.
For example is the increased secretion of cortisol, the
„”stress hormone”, by the adrenal cortex during a stress
response.
19. Down Regulation
When the plasma concentration of hormone is chronically
elevated, the total number of target-cell receptor for
hormone is gradually reduced as a direct result of the
effect a sustained elevation of hormone has on the hormone
receptors.
This phenomenon prevents the target cells from
overreacting to a prolonged high concentration of hormone.
20. Down Regulation
This down-regulation of the receptors can occur as a result of:
1. Inactivation of some of the receptor molecule.
2. Inactivation of some of the intracellular protein signaling
molecules.
3. Temporary sequestration of the receptor to the inside of the
cell, away from the site of action of hormones that interact with
cell membrane receptors.
4. Destruction of the receptors by lysosomes after they are
internalized.
5. Decreased production of the receptors.
In each case, receptor down-regulation decreases the target
tissue‟s responsiveness to the hormone.
21. Endocrine Disorders
Too Little Hormone Activity Too Much Hormone Activity
Too little hormone secreted by Too much hormone secreted by
the endocrine gland the endocrine gland
(hyposecretion)* (hypersecretion)*
Increased removal of the hormone Reduced plasma protein binding
from the blood of the hormone (too much free,
Abnormal tissue responsiveness to biologically active hormone)
the hormone Decreased removal of the
Lack of target-cells receptors hormone from the blood
Lack of an enzyme essential to Decreased inactivation
the target-cell response Decreased excretion
*Most common causes of endocrine dysfunction
22. Permissiveness
With permissiveness, one hormone must be present in
adequate amounts for the full exertion of another
hormone‟s effect.
In essence, the first hormone, by enhancing a target
cell‟s responsiveness to another hormone, “permits” this
other hormone to exert its full effect.
Example: thyroid hormones increases the number of
receptors for epinephrine.
23. Synergism
Synergism occurs when the actions of several
hormones are complementary and their combined
effect is greater than the sum of their separate
effects.
Example: FSH and testosterone are required for
maintaining the normal rate of sperm production.
24. Antagonism
Antagonism occurs when one hormone causes the
loss of another hormone‟s receptors, reducing the
effectiveness of the second hormone.
Example: progesterone inhibits uterine
responsiveness to estrogen during pregnancy, by
causing loss of estrogen receptors.