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:

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.

Mechanism of Protein Hormone Action

(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.

Mode of Hormone Action

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.

Mechanism of Steroid Hormone

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

Feed back Control Involving the Hypothalamus, Anterior Lobe of Pituitary Gland, Thyroid Gland and Target Tissues

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.

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