Hormone: Hormone as Messenger and Regulator

The secretion of all endocrine glands is termed as hormone (Gr. Hormoeine-to set in
motion).

It was first discovered by Bayliss and Starling in 1902. A hormone can be defined as “a
chemical substance produced in one part of the body and carried by blood to a target
organ where it regulates certain process.”

Therefore, hormones are informational molecules or chemical messengers that regulate

different biological processes of the body.

Hormones as Messengers and Regulators:

Hormones as Messengers:

On the ventral side of diencephalon (last part of fore brain) hypothalamus is present. It
consists of number of scattered masses of grey matter in the white matter. Masses of grey
matter containing neurons form hypothalamic nuclei. The neurons (neuro secretory cells)
of hypothalamic nuclei secrete several hormones called neuro hormones (releasing
factors) into the blood. Blood carries these neuro hormones to the anterior pituitary
where the neuro hormones stimulate pituitary to release various hormones. Thus, neuro
hormones act as messengers.

Feedback Control:

Hormones as Regulators (Feed Back Control):

This mechanism is known as homeostasis. Blood carries hormones from the endocrine
gland to the target organ. Decrease or increase in the amount of hormone in the blood
has an effect on the concerned gland (secreting gland) to reduce or increase the secretion
of the specific hormone. This mechanism is known as feedback control.

It is of two types:

(i) Positive feedback control and

(ii) Negative feedback control.

To understand the mechanism involved in feedback control, we can take case of thyroxine
secretion.

(i) Positive Feed Back Control:

Thyroxine hormone is secreted by thyroid gland. The thyrotropin releasing hormone (TRH)
from the hypothalamus stimulates the anterior pituitary to secrete thyroid stimulating
hormone (TSH). TSH in turn stimulates the tyroid gland to secrete thyroxine. If the level of
thyroxine in blood is less than normal, this low thyroxine level stimulates hypothalamus
to secrete more TRH. This results in increased secretion of TSH which in turn stimulates
increased secretion of thyroxine. Such regulatory mechanism is called positive feedback
control.

(ii) Negative Feed Back Control:

If the level of thyroxine in blood is more than the normal, this high thyroxine level
produces an inhibitory effect on hypothalamus. As a result less TRH and then less TSH are
produced by hypothalamus and anterior pituitary respectively. This results a decrease in
thyroxine. This is called negative feedback control.clip_image002

Mechanism of Hormone Action (With Feedback Regulation)

Let us make an in-depth study of the mechanism of hormone action with feedback
regulation of hormone production.

Mechanism of Hormone Action:

1. Enhancement of enzyme synthesis:

The steroid hormones and the thyroid hormones enter the cell and combine with the
specific receptor protein to form ‘receptor protein-hormone complex’. This complex will
then bind to a specific site on DNA and initiate or enhance the synthesis of mRNA which in
turn synthesizes the protein i.e. enzymes. Therefore the cell reactions speed up.

2. Change in cell permeability:

Hormones like insulin binds to a specific receptor on the cell membrane which results in
alteration of the permeability of the cell to certain substances like glucose, amino acids
and ions. The entry of these substances will bring a change in cell reactions.
3. Action through a second messenger (cAMP):

Hormones like epinephrine, glucagon bind to a regulatory site on the cell membrane. On
the inner side of this regulatory site, an enzyme known as adenyl cyclase is present that
converts ATP to cAMP which then activates certain protein kinases that in turn will
phosphorylate certain enzymes. Some enzymes on phosphorylation become active
whereas some other enzymes become inactive. Certain reactions are therefore stimulated
while others are inhibited.

Feedback Regulation of Hormone Production:

The production of hormones is regulated by feedback mechanism.

There are two types of feedback regulation:

(1) Negative feedback regulation and

(2) Positive feedback regulation.

1. Negative feedback regulation:

When the target hormone is in little excess, then this excess hormone will inhibit the
production of its tropic hormone. The tropic hormone in turn will stop the release of the
release factors. The inhibitory action of the tropic hormone over the release factor is
known as the short loop feedback. At other instances the target hormone can itself inhibit
the release factor this is known as long loop feed back.

2. Positive feedback regulation:

Estrogen stimulates the production of luteinizing hormone.

Secretion of hormones from endocrine glands:

The peptide hormones and the catecholamine’s are secreted by a process called
exocytosis. Steroid hormones are secreted by passive diffusion.

Circulation of hormones in blood:

The water soluble peptide hormones and the catecholamine’s circulate in free form in the
blood. Steroid and thyroid hormones circulate bound to specific proteins known as
binding, carrier or transport proteins ex Thyroxine binding globulin (TBG).

Degradation and excretion of hormones:

All the hormones are degraded and excreted. Peptide hormones are degraded in the liver
and/or kidney. The catecholamine’s, steroids and the thyroid hormones are inactivated
directly by enzymatic modification in the blood and/or in the liver.

Disorders of the endocrines:

There are three major classes of endocrine disorders:

1. Insufficient hormone production:

This may be due to abnormal function or destruction of the endocrine gland.

2. Excess hormone production:

This is due to tumors of the gland.

3. Altered tissue responsiveness to hormone effects:

(a) Immunity to hormones

(b) Defective or absence of receptor

(c) Inactive receptor hormone complex.

These are the causes that lead to ineffectiveness of hormones though they are produced
in normal amounts.

Mechanisms of Hormone Action: 2 Mechanisms

The following points highlight the two important mechanisms of hormone action. The
mechanisms are: 1. Mode of Protein Hormone Action through Extracellular Receptors 2.
Mode of Steroid Hormone Action through Intracellular Receptors.

Mechanism # 1. Mode of Protein Hormone Action through Extracellular Receptors:

(i) Formation of Hormone Receptor Complex:

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Every hormone has its own receptor. The number of receptors for each hormone varies.
Insulin receptors for most cells is less than 100 but for some liver cells their number may
be more than 1,00,000. The molecules of amino acid derivatives, peptides or polypeptide
protein hormones bind to specific receptor molecules located on the plasma membrane to
form the hormone receptor complex.

(ii) Formation of Secondary Messengers—the Mediators:

The hormone-receptor complex does not directly stimulates adenyl cyclase present in the
cell membrane. It is done through a transducer G protein. Alfred Gilmans has shown that
the G protein is a peripheral membrane protein consisting of ∝, β and γ subunits (Fig
22.19).

It interconverts between a GDP form and GTP form. In muscle or liver cells, the hormones
such as adrenaline bind receptor to form the hormone-receptor complex in the plasma
membrane.

The hormone- receptor complex induces the release of GDP from the G protein. The α-
subunit bearing GTP separates from the combined β and у subunits. The β and у subunits
do not separate from each other. The activated β and γ subunits of G protein activate
adenyl cyclase. The activated adenyl cyclase catalyses the formation of cyclic adenosine
monophosphate (cAMP) from ATP.
The hormone is called the first messenger and cAMP is termed the second messenger.

The hormones which interact with membrane-bound receptors normally do not enter the
taget cell, but generate second messengers (e.g., cAMP).

Besides, cAMP, certain other intracellular second messengers are cyclic guanosine
monophosphate (cGMP), diacyl-glycerol (DAG), inositol triphosphate (IP3) and Ca+
+
 responsible for amplification of signal. Earl W. Sutherland Jr (1915-1974) discovered
cAMP in 1965. He got Nobel prize in physiology of medicine in 1971 for his discovery,
“Role of cAMP in hormone action”.
(iii) Amplification of Signal:

Single activated molecule of adenyl cyclase can generate about 100 cAMP molecules. Four
molecules of cAMP now bind to inactive protein-kinase complex to activate protein-kinase
A enzyme. Further steps as shown in involve cascade effect. In cascade effect, every
activated molecule in turn activates many molecules of inactive enzyme of next category
in the target cell. This process is repeated a number of times.

In the cytoplasm a molecule of protein kinase A activates several molecules of

phosphorylase kinase. This enzyme changes inactive form of glycogen phosphorylase into
active one.

Glycogen phosphorylase converts glycogen into glucose-1 phosphate. The latter changes
to glucose. As a result single molecule of ademaline hormone may lead to the release of
100 million glucose molecules within 1 to 2 minutes. This increases the blood glucose
level.

(iv) Antagonistic Effect:

The effect of hormones which act against each other are called antagonistic effects. Many
body cells use more than one second messenger. In heart cells cAMP acts as a second
messenger that increases muscle cell contraction in response to adrenaline, while cGMP
acts as another second messenger which decreases muscle contraction in response to
acetylcholine.

Thus the sympathetic and parasympathetic nervous systems achieve antagonize effect on
heart beat. Another example of antagonistic effect is of insulin and glucagon. Insulin
lowers blood sugar level and glucagon raises blood sugar level.

(v) Synergistic Effect:

When two or more hormones complement each other’s actions and they are needed for
full expression of the hormone effects are called synergistic effects. For example, the
production and ejection of milk by mammary glands require the synergistic effects of
oestrogens, progesterone, prolactin and oxytocin hormones.

Mechanism # 2. Mode of Steroid Hormone Action through Intracellular Receptors (Fig.
22.20):

Steroid hormones are lipid-soluble and easily pass through the cell membrane of a target
cell into the cytoplasm. In the cytoplasm they bind to specific intracellular receptors
(proteins) to form a hormone receptor complex that enters the nucleus.

In the nucleus, hormones which interact with intracellular receptors (e.g., steroid
hormones, iodothyromines, etc.) mostly regulate gene expression or chromosome
function by the interaction of hormone-receptor complex with the genome.
Biochemical actions result in physiological and developmental effects (tissue growth and
differentiation, etc.). In-fact the hormone receptor complex binds to a specific regulatory
site on the chromosome and activates certain genes (DNA).

The activated gene transcribes mRNA which directs the synthesis of proteins and usually
enzymes in the cytoplasm. The enzymes promote the metabolic reactions in the cell. The
actions of lipid soluble hormones are slower and last longer than the action of water-
soluble hormones.

Role of Hormones as Messengers and Regulators (Role of Hormones in Homeostasis):

Hormones as Messengers [Hypothalamus-hypophysial (pituitary) Axis]:

Hypothalamus is a part of the fore brain. Its hypothalamic nuclei— masses of grey matter
containing neurons, are located in the white matter in the floor of the third ventricle of
the brain. The neurons (neurosecretory cells) of hypothalamic nuclei secrete some
hormones called neurohormones (releasing factors) into the blood.

The neurohormones are carried to the anterior lobe of the pituitary gland (= hypophysis)
by a pair of hypophysial portal veins. In the pituitary gland (hypophysis) the
neurohormones stimulate it to release various hormones. Hence the neurohormones are
also called “releasing factors”.

Hormones as Regulators (Feed Back Control):

Homeostasis means keeping the internal environment of the body constant. Hormones
help in maintaining internal environment of the body. When the secretion of hormones is
under the control of factors or other hormones it is called feedback control. The
regulation of secretion of thyroxine from the thyroid gland is an example of such feedback
control mechanism.

Feed back control is of two types:

(i) Positive Feed Back Control:

If the level of thyroxine is less than normal limits in the blood, thyroxine level stimulates
the hypothalamus to secrete more of TRH which results in increased secretion of TSH
which in turn stimulates increased secretion of thyroxine. Such regulatory effect is called
positive feedback control.

(ii) Negative Feed Back Control:

The thyrotropin releasing hormone (TRH) from the hypothalamus stimulates the anterior
lobe of the pituitary gland to secrete the thyroid stimulating hormone (TSH).

The TSH in turn stimulates the thyroid gland to secrete thyroxine. A high amount of
thyroxine in the blood exerts an inhibitory effect on hypothalamus in such a way that less
of TRH and TSH is produced respectively. This eventually results a decrease in thyroxine.
This is called negative feedback control.