MECHANISM OF HORMONAL ACTIONS LECTURER IN CHARGE BAMIDELE

MECHANISM OF HORMONAL ACTIONS LECTURER IN CHARGE BAMIDELE OLUBAYODE

INTRODUCTION • It is well known that the hormone do not act directly on the target organs. • They first bind to specific receptors at the target cells. • Any cells that lack receptors for the hormones do not respond. • Receptors for some hormones are located on/in the target: • cell membrane • cytoplasm • nucleus. • The receptors may be likened to a lock while the hormone is the key, which fits that lock.

INTRODUCTION CONT'D • A hormone combines with its receptor to initiate a cascade of reactions in the cell, with each stage becoming more powerfully activated so that even small concentrations of the hormone can have a large effect. • Hormonal receptors are very large protiens and hormones with the same molecular structure may produce overlapping physiological response. • Each receptor is often highly specific for a single hormone and this determines the type of hormone that will act on a particular tissue. • The target tissues that are affected by a hormone are those that contain its specific receptors.

The locations for the different types of hormone receptors • In or on the surface of the cell membrane. The membrane receptors are specific mostly for the protein, peptide, and catecholamine hormones. • In the cell cytoplasm. The primary receptors for steroid hormones are located mainly in the cytoplasm. • In the cell nucleus. The receptors for the thyroid hormones are situated in the nucleus.

Water-soluble hormone receptor activation: Water-soluble hormones, such as epinephrine, bind to a cellsurface localized receptor, initiating a signaling cascade using intracellular second messengers. Source: Boundless. com.

Lipid-soluble hormone receptor activation: Nuclear hormone receptors are activated by a lipid-soluble hormone such as estrogen, binding to them inside the cell. Lipid-soluble hormones can cross the plasma membrane. Source: Boundless. com.

The Control of Number and Sensitivity of Receptors • The number of receptor proteins in the target cells does not remain constant always. • It varies from minute to minute and day to day. • They are often inactivated or destroyed during the course of their function, and at other times they are reactivated or new ones are formed in the cell. • When increased hormone concentration and increased binding of hormone with its target cell receptors cause the number of active receptors to decrease, there is down-regulation of the receptors

The Control of Number and Sensitivity of Receptors Cont'd • Down-regulation of receptor decreases the responsiveness of the target cell to hormone and can occur due to: Ø inactivation of some of the receptor molecules. Ø inactivation of some of the intracellular protein signaling molecules. Ø temporary sequestration of the receptor to the inside of the cell, away from the site of action of hormones that interact with cell membrane receptors, Ø destruction of the receptors by lysosomes after they are internalized Ø decreased production of the receptors

The Control of Number and Sensitivity of Receptors Cont'd • Up-regulation of receptors occur when the stimulating hormone induces greater than normal formation of receptor or intracellular signaling molecules in the target cell. • It is also occur when greater number of available receptor interact with the hormone. • When this takes place, the target tissue becomes progressively more sensitive to the stimulating effects of the hormone.

Mechanism of actions of hormones • This is the way hormones act to produce their effects. Hormones act in this three ways: 1. change the membrane permeability 2. activation of intracellular enzymes 3. activation of intracellular genes • A hormone binds with its receptor to form hormone/receptor complex. The hormone/receptor complex activate cytoplasmic systems which then produce second messengers. The hormone itself is the first messenger.

SECOND MESSENGER MECHANISM • Many hormones exert their effects via the formation of second messenger within the target cell. • The hormone/receptor complex activates the enzyme adenyl cyclase. • Adenyl cyclase converts ATP to 3'5'-adenosine monophosphate (c. AMP). • c. AMP is the second messenger which brings about the physiological response in the target cell. • The nature of the response depends on the nature of the target cell since the second messenger is used by many different cells yet different responses are obtained.

Source: Gandham Rajeev

ACTIONS OF c. AMP • It causes all or most of the intracellular effects of the hormones. • The only direct effect the hormone has on the cell is to activate its specific membrane receptor. • c. AMP actions include: 1. activation of intracellular enzymes 2. alteration of cell permeability 3. causes muscle contraction and relaxation 4. causes protein synthesis and secretion of other substances

OTHER SECOND MESSENGERS • The other important substances that act as second messenger for different hormones are: ü Calcium ions and calmodulin ü Products of membrane phospholipid breakdown (inositol trisphosphate and diacylglycerol) ü Cyclic guanosine-3'5'-monophosphate (c. GMP)

Mechanism of action of steroid hormones • The steroid hormones are lipid soluble, they enter the cell cytoplasm and bind with specific receptor protein. • The hormone/receptor complex formed diffuses into or is transported into the nucleus of the cell. • Within the nucleus of the cell, the complex combines with nuclear DNA and activates specific genes to form messenger RNA (m. RNA). • m. RNA moves into the cytoplasm to promote the formation of new proteins. • The new proteins produce the actions of the hormones.

Source: Shashi Kant

Thyroid hormone mechanism of action • Thyroxine and triiodothyronine enter the cells and binds to receptors in the cell nucleus. • They activate the genetic mechanism for the formation of many different types of intracellular proteins. • Many of the intracellular proteins are enzymes which enhanced metabolic activities in the most cells of the body.

Source: Danish Hassan

References • Guyton and Hall. Textbook of Medical Physiology. 9 th Edition, W. B Saunders company, London, Toronto. Philadelphia. • Oyebola D. O. (2002)Essential Physiology for students of Medicin e, dentistry, Pharmacy and Related disciplines. Volume 1. • Boundless Anatomy and Physiology. Boundless. com

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