Essay on Hormones: Characteristics and Mechanism

In this article we will discuss about the Hormones:- 1. Definition of Hormones 2. General Characteristics of Hormones 3. Classification 4. Mechanism of Action 5. Assay 6. Chemistry and Functions.

Contents:

1. Essay on the Definition of Hormones
2. Essay on the General Characteristics of Hormones
3. Essay on the Classification of Hormones
4. Essay on the Mechanism of Action of Hormones
5. Essay on the Assay of Hormones
6. Essay on the Chemistry and Functions of Hormones

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Essay # 1. Definition of Hormones:

The chemical substance or messenger is produced from one part of body by endocrine gland, enters into the circulation, earned to distal target organ or cell to modify their structure and function is called hormone.

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Essay # 2. General Characteristics of Hormones:

The endocrine or ductless glands secrete hormones which catalyse and control metabolic processes.

The hormones differ from enzymes in the follow­ing ways:

i. The hormones are produced in an organ in which they ultimately perform their function.

ii. They are secreted into the blood prior to use.

iii. Structurally, they are not always proteins.

The action of a hormone at a large organ is regulated by 5 factors:

(a) Rate of synthesis and secretion of the stored hormone from the endocrine gland.

(b) Specified transport systems in the plasma.

(c) Hormone-specific receptors in target cell cytosol or membranes.

(e) Ultimate degradation of the hormone, usu­ally by the liver or kidneys.

Receptor:

Chemical signals like hormone molecules reach the target cells where they become bound by receptors. Receptors are protein macro- molecules and glycoprotein in nature. A ligand is a substance which can combine with the receptor. A ligand, thus may be a hormone or drug molecule.

Agonist:

Each type of receptor is specific for corresponding type of ligand. So the post receptor event will occur and this type of ligand is called agonist.

Antagonist:

They are the blocks which have close chemical structure with the agonist molecule, so the antagonist molecule can and do occupy the receptor site but there is some structural difference also so that post receptor events do not occur and because of the fact that the receptor sites are now occupied, the agonist molecules cannot occupy the P sites.

Receptors which bind the peptide hormones are present on the cell membrane, that is they partly protrude in the ECF and partly remain within the membrane, such receptors are called membrane bound receptors. Receptors for thyroid and steroid hormones are called cytosol receptors because they occur either in the cytosol or on the nucleus.

The receptor has two domains:

i. Recognition domain—binds hormone.

ii. Coupling domain—generates signal.

Based on their chemical structures, the hor­mones have been classified.

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Essay # 3. Classification of Hormones:

According to location of receptor:

i. Membrane bound receptor.

ii. Intracellular receptor.

Steroid hormone (Oestrogen, progester­one, androgen, glucocorticoid). Thyroid hormone—T3, T4.

iii. Calcitriol.

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Essay # 4. Mechanism of Action of Hormones:

Hormones that Bind to Intracellular Receptor:

i. These types of hormones are lipophilic in nature, so they can diffuse through the plasma membrane of all cells. The steroid hormone has a specific soluble, oligomeric receptor protein (mobile receptor) either in the cytosol and/or inside the nucleus.

ii. The hormone-receptor complex next un­dergoes a temperature and salt dependent activation reaction that results in size, con­formation and surface charge changes to favour its binding to the nuclear chroma­tin attached to nuclear matrix.

iii. The hormone receptor complex binds to a specific region of DNA (called the hormone response element) and activates or inactivates specific genes.

iv. Promoter element is generic since it is present in some form or other in all genes. This element specifies the site of RNA polymerase II attachment of DNA and so the accuracy of transcript initiation.

v. A second element, the hormone response element has been identified in many genes regulated by steroid hormones. The ele­ment modulates the frequency of transcript initiation and is less dependent on posi­tion and orientation, so it resembles the transcription enhancer elements found in other genes.

Hormones that Bind to Cell Membrane Receptor:

A. cAMP as the Second Messenger:

i. For the formation of cAMP from ATP needs: Receptor, GS protein, Adenylate cyclase.

ii. cAMP (Cyclic adenosine 3′-5′ monophos­phate) is formed from ATP by the action of the enzyme adenylate cyclase and con­verted to physiologically inactivated 5′- AMP by the action of enzyme phosphodi­esterase.

iii. Hormone receptor complex combines with G_s or G_i; (s = stimulatory, i = inhibitory) type of GTP dependent trimeric nucleotide regulatory complex of the cell membrane.

iv. Both G_s or G₁ are made up of 3 subunits. G_s contains α_sβγ and G_i contains α_iβγ.

v. The α subunit (either G_s or G_i) is bound to GDP. When binding of hormone to R_s or R_i results in a receptor-mediated activa­tion of G, then GDP is exchanged for GTP and the a subunit separates from the com­bined β and γ subunits.

vi. This GTP-α_s activates effectors (adenylate cyclase). The intrinsic GTPase activity of the α-subunit then converts GTP and GDP and leads to re-association of the a with βγ subunit.

vii. On the other hand, α_i-GTP inhibits adenylate cyclase by binding with it. This lowers the intracellular concentration of cAMP

Hormones that stimulate adenylate cyclase: ACTH, ADH, FSH, Glucagon. Hormones that inhibit adenylate cyclase: Acetylcholine, Angiotensin II.

viii. cAMP binds to a protein kinase that is a hetero terameric molecule consisting of 2 regulatory subunits (R) and 2 catalytic subunits (C). cAMP binding results in the following reaction.

4cAMP + R₂C₂ ⇌ R₂ (4cAMP) + 2C

ix. The R₂C₂ complex has no enzymatic activity but the binding of cAMP by R dissociates R from C, thereby activating protein kinase. This activated protein kinase catalyzes the transfer of the y phosphate of ATP (Mg⁺⁺) to a serine or threonine residue in a variety of proteins. Thus they regulate the conformational changes of phosphoprotein and physiologic effect occurs.

B. Role of cGMP in Hormone Action:

i. Hormones such as insulin and growth hormone, affect the guanylate cyclase cGMP system. This will increase the intracellular concentration of cGMP and activate cGMP dependent protein kinases.

ii. The active cGMP protein kinase would in turn bring about phosphorylation of specific cellular proteins to change their activities, leading to relaxation of smooth muscles, vasodilatation and other effects.

iii. The idea of cGMP as second messenger has not been accepted as yet. It is likely that Ca⁺⁺ may act as second messenger to activate guanylate cyclase and thereby increasing the concentration of cGMP inside the cell.

iv. It appears that cGMP has its unique place in hormone action. The atriopeptins, a family of peptides, produced in cardiac atrial tissues cause natriuretic, diuresis, vasodilatation and inhibition of aldosterone secretion.

v. These peptides (e.g., atrial natriuretic fac­tor) bind to and activate the membrane bound form of guanylate cyclase. This re­sults in an increase of cGMP.

C. Role of Calcium in Hormone Action:

i. It is suggested that ionized calcium of the cytosol is the important signal for hormone action than cAMP.

ii. The extracellular calcium (Ca⁺⁺) concen­tration is about 5 mmol/L, the intracellu­lar concentration of this free ion is much lower 0.1-10 µmol/L.

iii. The hormones that bind cell membrane receptor enhance membrane permeability to Ca⁺⁺ and thereby increase Ca⁺⁺ influx. This is probably accomplished by an Na⁺/Ca⁺⁺ exchange mechanism that has a high capacity but a low affinity for Ca⁺⁺. There is a Ca²⁺/2H⁺-ATPase dependent pump that extrudes Ca²⁺ in exchange for H⁺. This has a high affinity for Ca²⁺ but a low ca­pacity.

iv. Cell surface receptors such as those for ace­tylcholine, ADH, when occupied by their respective ligands, potent activators of phospholipase c.

v. Receptor binding and activation of phos­pholipase c are coupled by a unique G protein.

vi. Phospholipase c catalyses the hydrolysis of phosphatidylinositol 4, 5-bisphosphate to inositol triphosphate and 1, 2 diacylglcerol.

vii. The diacylglycerol is itself capable of ac­tivating protein kinase c, the activity of which also depends upon free ionic cal­cium.

viii. Inositol triphosphate is an effective releaser of calcium from intracellular stor­age sites such as endoplasmic reticulum, and mitochondria.

ix. Thus, the hydrolysis of PIP₂ leads to acti­vation of protein kinase c and promotes an increase of cytoplasmic calcium ion.

x. The calcium dependent regulatory protein is now referred to as calmodulin. Calmodulin has 4Ca⁺⁺ binding sites. Ca⁺⁺– calmodulin complex can activate specific kinases. These then modify the conforma­tional changes of phosphoprotein and al­ters physiologic responses.

xi. The activated protein kinase c can phosphorylate specific substrates and alter physiologic processes.

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Essay # 5. Assay of Hormones:

A. Biologic Assays:

i. Biologic assays measure the levels of func­tional activity of hormones.

ii. These assays are not usually specific due to lack of sensitivity.

B. Chemical Assays:

i. These assays measure the absolute quan­tity of a given hormone.

ii. These are not generally applicable in case of protein hormones.

C. Radio-displacement Chemical Assays:

i. These assays are largely used nowadays for protein and non-protein hormones.

ii. The binding protein is a specific anti­body, membrane receptor or serum trans­port protein. The un-labelled hormone, present as standard or unknown, displaces the labelled hormone and results in the increase in radioactivity in the unbound fraction. These include electrophoresis and preferential salt precipitation.

iii. These assays are more sensitive than most bioassays because the concentrations of less than lng/ml can be detected by these assays.

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Essay # 6. Chemistry and Functions of Hormones:

The Pituitary Gland:

i. The human pituitary is located in the brain just behind the optic chiasma as an exten­sion from the floor of the hypothalamus and is about 10 mm in diameter.

ii. The average weight of human pituitary is 0.5-0.6 gm. in males and 0.6-0.7 gm. in fe­males.

iii. It consists of two parts:

(a) The adenohypophysis or anterior lobe;

(b) The neurohypophysis or posterior lobe.

Role of Hypothalamus:

i. The regulatory factors secreted by the hypothalamus control the secretion of hormones by the pituitary gland. The regu­latory factors are considered to be hor­mones.

ii. In addition to the secretion of regulatory hormones, neurophysial hormones are ac­tually synthesized in the hypothalamus and migrate as granules down the nerve fibres and accumulate at the nerve end­ings from which they are secreted.