MECHANISM OF HORMONE ACTION

Mechanism of Hormone Action:

              Introduction:

·      Hormones are natural organic substances that regulate growth, metabolism and other function of an  organism.

·      Hormones are secreted chemical messenger that enables communication between cells and tissues throughout the body.

·      Hormones are secreted by glands of the endocrine system and they serve to maintain homeostasis and to regulate numerous other system and processes include reproduction and development.

·      They are simply biochemical messenger.

·      They can be classified according to the chemical composition, organs they work Example, Reproductive hormones in the reproductive organs and if they either act on the same cell producing them i.e. autocrine and paracrine.

General principles of hormone action:

·      Trophic hormone: A hormone that has its primary function, the regulation of hormone secretion by another endocrine gland.

·      Synergism: When different hormones work together and have a greater effect than individual hormone action.

·      Permissiveness: A small amount of one hormone allows a second hormone to have its full effect on target cell i.e. first hormone permits the fuel action of the second hormone.

·      Antagonist: One hormone produces the opposite effect on the action of other. The processes involve both negative and positive feedback. For example; if A>B>C>D, increase in D causes inhibition of A i.e. negative feedback; if D decreases, production of A is triggered, this is a positive feedback

General characteristics of Hormone:

·      Hormones are not secreted at a uniform rate.

·      It exerts their effects in bio-catalytic amounts.

·      Turnover is varied and usually rapid.

·      They exert multiple actions.

·      Hormones exhibit high degree of specificity.

·      Different tissues may respond differently to a given hormone.

Mechanism of Hormone Action:

We will discuss how protein hormones and lipid hormones perform their action.

        I.         Mode of protein hormone action through extracellular receptors: 

A.   Formation of hormone receptor complex:

Every hormone has its own receptor. The number of receptors for each hormone varies. Insulin receptors for most cells are less than 100 but for some liver cells their number may be more than one lakh. The molecule of amino acid derivatives derivatives, peptides or polypeptides protein hormone bind to specific receptor molecule located on the plasma membrane to form the hormone -receptor complex.

B.   Formation of secondary messengers – the mediators:

The hormone receptor complex does not directly stimulate adenyl cyclase present in the cell membrane. It is done through the transducer G- protein is a peripheral membrane protein consisting of alpha, beta and gamma subunits. It interconverts between GDP form and GTP form. In muscles or liver cells, the hormones such as adrenalin 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 alpha subunit bearing GTP separates from the combined beta and gamma subunits. The beta and gamma subunits do not separate from each other. The activated beta and gamma subunits of G proteins activate adenyl cyclase. The activated adenyl cyclase catalyzes the formation of cyclic adenosine mono phosphate (c AMP) from ATP.

The hormone is known as first messenger and c AMP is termed as second as second messenger.

ATP ----------→ c AMP + Pi

The hormones which interact with membrane bound receptors normally do not enter the target cell but generate second messenger. Besides c AMP, certain other intracellular second messengers are c AMP and diacyl- glycerol (DAG), ionositol triphosphate (IP3) and Ca ⁺2 responsible for amplification of signal. Earl W. Sutherland discovered c AMP in 1965. He got Nobel Prize in physiology of medicine in 1971 for his discovery.

C.   Amplification of signal:

Single activated molecule of adenyl cyclase can generate about 100 c AMP molecule. Four molecule of c AMP bind to inactive PK complex to activate PK A enzyme. Further steps involve cascade effect. In this effect, every activated molecule in turn activates many molecule of inactive enzyme of next category in target cell. This process is repeated number of times. In the cytoplasm a molecule of PK A activates several molecule of phosphorylase kinase. This enzyme changes inactive form of glycogen phosphorylase into active one.

Glycogen ----------→Glucose 1 phosphate ----------→ Glucose

                  Glycogen

                  Phosphorylase

As a result, single molecule of adrenaline hormone may lead to the release of 100 million glucose molecule within 1-2 minutes. This increases the blood glucose level.

D.   Antagonistic effect:

The effects of hormone which act against each other are called antagonistic effect. Many body cells use more than second messenger. In heart cells c AMP acts as second messenger that increases muscle cell contraction in response to adrenaline, while c GMP acts as another second messenger which decreases muscle contraction in response to acetylcholine. Thus, the sympathetic and parasympathetic nervous system achieves antagonistic effect on heart beat. Another complex of antagonistic effect is of insulin and glycogen. Insulin lowers blood sugar level and glycogen raises blood sugar levels.

E.    Synergistic effect:

When two or more hormones complement each other’s action 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 oxytoxin hormone.

                  

      II.         Mode of steroid hormone action through intracellular receptor:

Steroid hormones are lipid soluble and can 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 (eg; steroid hormone, iodothronines 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 an differentiation). Infact, the hormone receptor complex binds to specific regulatory site on the chromosome and activates certain genes. The activated genes transcribe m RNA which direct the synthesis of proteins and usually enzyme in the cytoplasm. The enzyme promotes the metabolic reaction in the cell. The action of lipid soluble hormones is slower and last longer than the action of water soluble hormones.

                    

Mode of Hormone Action:

Hormones perform their function in two ways:

A.   Synthesis of new protein molecule

B.   Changing cell permeability

Types of Receptor:

         i.         Membrane Receptor:

 Receptors present in or the surface of the cell membrane. Protein and peptide hormones, catecholamines like

Types of membrane receptor:

a.    Ion channel linked receptor

b.   G- Protein coupled receptor

c.    Enzyme linked receptor: Protein, peptide and catecholamine.

       

       ii.         Cytoplasmic Receptor:

Receptors present in the cytoplasm of cell. For example, steroid hormone

      iii.         Nuclear receptor:

 These are the receptor present in the nucleus and there is direct association with one or more chromosomes. For example, Thyroid hormone, Retinoid hormone, vitamin D.

     iv.         Lipid soluble receptor:

These receptors bind to specific cell receptor in the cell membrane and form hormone cell receptor complex which diffuses to nucleus. The receptor is eventually released for re- use. Steroid activates a specific gene to produce m RNA, m- RNA pass out into the cytoplasm and initiates protein synthesis.

Hormone Signalling:

The glands of the endocrine system secrete hormones directly into the extracellular environment. The hormones then diffuses to the bloodstream via capillaries and are transported to the target cells through the circulatory system This allows hormones to affect tissues and organs from the site of production or to apply systemic affect to the whole body.

Hormones producing cells are typically specialized and reside within a particular endocrine gland, such as thyrocytes in the thyroid gland. Hormones exit their cells of origin through the process of exocytosis or by other means of membrane transport.

Cellular recipients of a particular hormonal signal may be one of several cell types that reside within a number of different tissues. This is in the case of insulin which triggers a diverse range of systemic physiological effects. Different tissues types may also respond differently to the same hormonal signal. Hormones activate target cells by diffusing through the plasma membrane of the target cells (lipid soluble hormone) to bind a receptor protein within the cytoplasm of the cell or by binding a specific receptor protein in the cell membrane of the target cell (water soluble protein) In both cases, the hormone complex will activate a chain of molecular events within the cells that will result in activation of gene expression in the nucleus.

The reaction of the target cells may then be recognized by the original hormone producing cells, leading to down regulation in hormones production This is an example of homeostatic negative feedback loop.

                    

Steps of Hormone Signalling:

·      Biosynthesis of particular hormone in a particular tissue.

·      Storage and secretion of hormones.

·      Transport of hormone to the target cells, tissues or organs.

·      Recognition of the hormone by an associated cell membrane or an intracellular receptor protein.

·      Relay and amplification of the received hormonal signal via a signal transduction process.

·      Potential feedback to a hormone producing cell.

Hormone Classes:

The hormones fall into two general classes based on their solubility in water.

A.   Hydrophillic hormones:

They are water soluble hormone which is transported simple dissolved in blood.

For example; Catecholamines (Epinephrine and nor- epinephrine) and peptide or protein hormone.

B.   Lipophillic hormones:

They are poorly soluble in water. So, they cannot be dissolved in water, blood. They bind to plasma protein and present in the blood in protein bound form. They are lipid soluble hormone.

For example: Thyroid hormone, steroid hormone and Vitamin D3.

Classes of hormones are divided into three classes

1)   Peptide Hormones:

These are the hormones that are modified amino acid or short peptide or long protein chain of amino acid. Additionally, they contain carbohydrate moieties.

2)   Lipid hormones:

Steroid hormones that contain lipids synthesized from cholesterol and eicasanoids that contain lipid synthesized from the fatty acid chains of phospholipids that are found in the plasma membrane.

3)   Monoamines:

Hormones that are derived from aromatic amino acids such as phenylalanine, tyrosine and tryptophan are known as monoamines.

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