Medical Significance Of Hormones In The Endocrine System: Their Metabolism, Actions And Receptors
Endocrine disorders result from excessive or diminished secretion of hormones, or abnormalities in responsiveness of tissues. Progressive rise in hormone levels may reduce tissue sensitivity (negative co0operativity).
Synthesis, storage, release and transport of the site of action are the processes undergone before a hormone activates its target. After exerting their effects, the hormones are metabolized to inactive products or they are continually excreted. The concentration of a hormone in blood is governed both by its rate of synthesis and elimination. Many hormones function in closed loop systems, i.e. rise in level of the hormone in the blood exerts feedback inhibition on its controlling hormone. Many endocrine glands exhibit diurnal rhythmicity (sleep-wake cycle), pulsatility with regular periodicity, and regulation of secretion in response to substrate augmentation.
Hormones (like steroid hormones and thyroid hormones) are bound to carrier proteins of high affinity for transport. The hormone is biologically inactive in the bound form and it has to be split to restore its activity.
Hormones modulate both the intracellular and extracellular activities of cells so that the different cells in an organ or tissue behave as a synchronous macrocellular complex. As a general rule, hormones do not initiate biochemical processes primarily, but only regulate the rate of the reactions in responsive cells. Hormones produce measurable specific effect in organs, cells, cellular organelles, enzymes, genes or membranes. The specificity of hormone response is achieved by three mechanisms such as :
- Specific target tissue
- Appropriate receptor stimulation and
- The capacity of the cells to respond specifically to receptor activation.
Hormone effects are generally brought about by conformational changes in protein molecules of the receptors or enzymes in the target cell. The hormonal effect often leads to acceleration of some biochemical reactions or metabolic pathways with inhibition of others.
One of the main functions of the endocrine system is communication of information between cells. Polypeptide hormones and catecholamines act on the cell surface through specific receptors and activate intracellular second messengers like cyclic AMP and Ca++ or enzymes. These in turn regulare the activities of the cell. Peptide hormones bring about rapid responses in tissues within seconds or minutes.
Steroid hormones exert their action within the cell by influencing specific receptors which bind to nuclear chromatin. The hormone receptor complex regulates protein synthesis. Thyroid hormones enter the target cells and bind directly to receptor proteins in the chromatin. Such interaction which affects nuclear processes are relatively slow, taking a few hours.
The responsive cells contain specific sites of binding for active hormones. The hormones bring about their effect or response in target cells through the receptors. The binding to receptors takes place very quickly. Loss of cellular receptors leads to unresponsiveness to the hormone. Changes in receptor affinity or number also modify the magnitude of hormone responses. The biological effects of any hormone depends on:
- Its affinity for receptors
- Intrinsic agonist property,
- Its concentration at the site of action, and
- Its rate of degradation.
The number of hormone receptors on a cell far exceeds that required for bringing about a response. When 5-10% of available binding sites on the cells are occupied, the hormones exert their maximal effect. The remaining number act as spare receptors. Receptors have strict structural specificity, saturability, high affinity and often tissue specificity for target cell responsiveness. The surface receptors are regulated by metabolites such as cyclic GMP within the cell. At times, the receptors may become antigenic and stimulate the production of antibodies. These antibodies react with the receptors and interfere with their functions.
Hormone agonists (optimal inducers) are substances which directly stimulate hormone substances which directly stimulate hormone action by stabilization of hormone-receptor complex in an active conformational state. Hormone antagonists (anti-inducers) specifically block the effect of an agonist by binding with hormone receptors.
© 2014 Funom Theophilus Makama