HORMONES – MECHANISM OF ACTION AND REGULATION OF SECRETION

Hormones regulate target cells by binding to specific protein receptors. Their mechanism of action depends on whether they are lipid soluble or water soluble.

MECHANISM OF HORMONE ACTION

Hormones exert their action through receptors. These receptors are present on target cells. Only cells with receptors for a specific hormone respond, while cells lacking the specific receptors are unaffected. Receptors found on target cell membrane are called external receptors. Receptors present within the cytoplasm and nucleus are termed internal receptors.

Various hormones interact in different ways with their receptors. Polypeptide hormones bind to a fixed receptor at the outer cell surface. Steroid hormones bind to a specific mobile receptor in the cytoplasm. Thyroid hormones combine with a nuclear receptor.

When high concentrations of a hormone is present, target cells respond by decreasing the number of receptors on the cell surface.

Hormones exhibit their action by two mechanisms :

• Cyclic AMP (cAMP) mediated hormone activity
• Transcription and translation effects

cAMP MEDIATED HORMONE ACTIVITY

Hormones that act by this mechanism are – most proteins and polypeptide hormones, many amino acid derivatives and some prostaglandins.

These hormones bind to specific receptor site on outer surface of cell membrane. They act as first messenger. This causes activation of the enzyme adenylyl cyclase on the inner surface of cell membrane. This increases the formation of intracellular cAMP from ATP.

cAMP is the second messenger. cAMP is a basic regulator of cell metabolism. It acts by converting inactive protein kinases to their active form. Protein kinases catalyze phosphorylation of proteins, thereby altering their form and action.

cAMP exerts action signaled by hormone. It may cause different functions in different target cells, such as :

• Alter permeability of membrane to different substances or ions.
• Activation or inactivation of rate limiting enzymes.
• Increase or decrease in protein synthesis by acting on ribosomes.
• Regulation of release of hormones from endocrine gland.

TRANSCRIPTION AND TRANSLATION EFFECT

Steroid hormones, 1, 25 DHCC and thyroid hormones act by this mechanism. These hormones are lipid soluble and can easily enter into target cells. Upon entering the cell, these hormones bind to their specific cytoplasmic receptor.

The hormone – receptor complex enters the nucleus and gets attached to chromatin. The complex then interacts with DNA to stimulate transcription of a particular gene. This leads to increase in synthesis of specific mRNA (messenger RNA). The specific mRNA then enters cytoplasm where it synthesizes specific proteins by the process of translation. The proteins then perform their function.

REGULATION OF SECRETION OF HORMONES

DIRECT CONTROL

Some amount of hormone secretion is regulated directly by the concentration of substances upon which hormones act. For example, a rise in blood glucose levels stimulates insulin secretion from pancreas. Whereas a fall in blood glucose promotes secretion of glucagon from pancreas.

NERVOUS CONTROL

Neurotransmitters released by neurons mediate the effects of hormones. Neural control of endocrine glands occurs by three mechanisms :

a) Direct innervation by autonomic nervous system : For example, Pancreatic islets of Langerhans receive postganglionic parasympathetic innervation. Adrenal medulla is innervated by preganglionic cholinergic (sympathetic) fibers.

b) Control of posterior pituitary via neurosecretory neurons : Acetylcholine released at synapses of of neurons of posterior pituitary gland causes release of ADH and oxytocin.

c) Control of anterior pituitary via neurosecretory neurons : The peptidergic neurons of anterior pituitary secrete specific releasing factors. These releasing factors stimulate or inhibit the secretion of anterior pituitary hormones into bloodstream.

FEEDBACK REGULATION

Feedback mechanism of hormones is a phenomenon where the production of a hormone is regulated by the amount of hormone. Thus, it is a self regulating process which can be negative feedback (more common) or positive feedback (less common).

NEGATIVE FEEDBACK – When hormone levels become too high, further secretion is inhibited.

For example, increased blood glucose after carbohydrate intake stimulates release of insulin. Insulin then promotes uptake of glucose by cells and blood glucose levels fall. The drop in blood glucose then signals pancreas to stop releasing insulin.

TSH (thyroid stimulating hormone) released by pituitary gland triggers thyroid hormone secretion from thyroid gland. When levels of thyroid hormone in blood becomes too high, TSH release is inhibited to decrease thyroid hormone output.

POSITIVE FEEDBACK – In positive feedback, hormone secretion is amplified by stimulus until a specific event is completed. For example, during labor, the stretching of cervix triggers release of oxytocin. Oxytocin causes stronger uterine contractions and further stretching of cervix, stimulating more oxytocin release. This cycle continues till delivery occurs, after which the process stops.