Glucocorticoids – Definition, Types, Functions

Glucocorticoids

Glucocorticoids are corticosteroids that act mainly on glucose metabolism.

Glucocorticoids are:

1. Cortisol
2. Corticosterone
3. Cortisone.

Glucocorticoids Source Of Secretion: The glucocorticoids are secreted mainly by zona fasciculata of adrenal cortex. A small quantity of glucocorticoids is also secreted by zona reticularis.

Glucocorticoids Chemistry And Half-Life: Glucocorticoids are C₂₁ steroids having 21 carbon atoms. The half-life of cortisol is 70-90 minutes and that of corticosterone is 50 minutes. The half-life of cortisone is not known.

Read And Learn More: Medical Physiology Notes

Daily Output And Plasma Level: The daily output and plasma level of glucocorticoids are given in Table.

Functions Of Glucocorticoids: Cortisol or hydrocortisone is more potent and it has 95% of glucocorticoid activity. Corticosterone is less potent showing only 4% of glucocorticoid activity. Cortisone with 1% activity is secreted in minute quantity.

Glucocorticoids – Life Protecting Hormone

• Like aldosterone, cortisol is also essential for life but in a different way. Aldosterone is a life saving hormone, whereas cortisol is a life-protecting hormone because it helps to withstand the stress and trauma in life.
• Glucocorticoids have metabolic effects on carbohydrates, proteins, fats, and water. These hormones also show mild mineralocorticoid effects. The removal of adrenal glands in human beings and animals causes disturbances of metabolism. Exposure to even mild harmful stress after adrenalectomy leads to collapse and death.

1. On Carbohydrate Metabolism: Glucocorticoids increase the blood glucose level by two ways:
   1. By promoting gluconeogenesis in liver from amino acids: Glucocorticoids enhance the breakdown of proteins in extrahepatic cells, particularly the muscle. It is followed by release of amino acids into circulation. When the amino acids enter the liver from the blood, gluconeogenesis occurs
   2. By inhibiting glucose uptake and utilization by peripheral cells: This action is called the anti-insulin action of glucocorticoids.
      • The hypersecretion of glucocorticoids increases the blood glucose level resulting in hyperglycemia, glucosuria, and adrenal diabetes.
      • Hyposecretion of these hormones causes hypoglycemia And fasting during adrenal insufficiency will be fatal. It decreases blood glucose level to a great extent resulting in death.
2. On Protein Metabolism: Glucocorticoids promote the catabolism of proteins. Glucocorticoids decrease the proteins in the cell and increase plasma amino acids and protein content in liver by the following methods:
   • In the body cells except liver cells, glucocorticoids decrease protein synthesis by inhibiting amino acid transport into the cells and by inhibiting the formation of RNA
   • At the same time, glucocorticoids accelerate protein catabolism and release of amino acids from the tissues
   • Glucocorticoids increase the transport of amino acids into hepatic cells. In hepatic cells, the amino acids are used for the synthesis of proteins, plasma proteins, and for gluconeogenesis.
     • Thus, glucocorticoids cause the mobilization of proteins from tissues other than liver. In hypersecretion of glucocorticoids, there is excess catabolism of proteins resulting in muscular wasting and negative nitrogen balance.
3. On Fat Metabolism: Glucocorticoids cause mobilization and redistribution of fats. The actions on fats are:
   1. Mobilization of fatty acids from adipose tissue
   2. Increasing the concentration of fatty acids in blood
   3. Increasing the utilization of fat for energy.
      • Glucocorticoids decrease the utilization of glucose. At the same time, these hormones mobilize fats and make the fatty acids available for utilization by which energy is liberated. It leads to the formation of a large amount of ketone bodies. It is called the ketogenic effect of glucocorticoids.
      • Hypersecretion of glucocorticoids causes an abnormal type of obesity by increasing the deposition of in certain areas such as the abdomen, chest, face, and buttocks.
4. On Water Metabolism: Whenever a large quantity of water is taken, glucocorticoids accelerate the excretion of water. Thus, glucocorticoids play important role in the maintenance of water balance. Adrenal insufficiency causes water retention and water intoxication after water load.
5. On Mineral Metabolism: Glucocorticoids enhance the retention of sodium and to lesser extent increase the excretion of potassium. Thus, hypersecretion of glucocorticoids causes edema, hypertension, hypokalemia, and muscular weakness. Glucocorticoids decrease blood calcium by inhibiting absorption from the intestine and increasing the excretion of calcium through urine.
6. On Bone: Glucocorticoids stimulate the bone resorption (osteoclastic activity) and inhibit bone formation and mineralization (osteoblastic activity). So in hypersecretion of glucocorticoids, osteoporosis occurs.
7. On Muscles: Glucocorticoids increase the release of amino acids from muscle by catabolism of proteins. So, hypersecretion causes muscular weakness due to negative nitrogen balance and hypokalemia.
8. On Blood Cells: Glucocorticoids decrease the number of circulating eosinophils by increasing the destruction of eosinophils in reticuloendothelial cells. These hormones also decrease the number of basophils, and lymphocytes and, increase the number of circulating neutrophils, RBCs, and platelets.
9. On Vascular Response: The presence of glucocorticoids is essential for the constrictor action of adrenaline and noradrenaline. In adrenal insufficiency, the blood vessels fail to respond to adrenaline and noradrenaline leading to vascular collapse.
10. On Central Nervous System: Glucocorticoids are essential for normal functioning of nervous system. Insufficiency of these hormones causes personality changes like irritability and lack of concentration. Sensitivity to olfactory and taste stimuli Increases in adrenal insufficiency.
11. Permissive Action of Glucocorticoids: Permissive action of glucocorticoids refers to the execution of actions of some hormones only in the presence of glucocorticoids. Examples are:
    1. Calorigenic effects of glucagon
    2. Lipolytic effects of catecholamines
    3. Pressor effects of catecholamines
    4. Bronchodilatation by catecholamines.
12. On Resistance to Stress
    • The exposure to any type of stress, either physical or mental, increases the secretion of adrenocorticotropic hormone (ACTH). ACTH in turn increases glucocorticoid secretion. The increase in glucocorticoid level is very essential for survival, as it offers high resistance to the body against stress.
    • The adrenalectomized animals die when exposed to stress. Exposure to stress in adrenal insufficiency is fatal in human beings also.
    • It is not known, how glucocorticoids increase the resistance to stress. It is assumed that the glucocorticoids enhance the resistance by the following ways:
      1. Immediate release and transport of amino acids from tissues to liver cells for synthesis of new proteins and other substances which are essential to withstand the stress
      2. Release of fatty acids from cells for the production of more energy during stress
      3. Enhancement of vascular reactivity to catecholamines and fatty acid mobilizing action of catecholamines, which are necessary to withstand the stress
      4. Prevention of severity of other changes in the body caused by stress.
13. Anti-inflammatory Effects
    • The knowledge of process of inflammation is necessary to understand the anti-inflammatory actions of glucocorticoids.
    • Inflammation is defined as a localized protective response induced by injury or destruction of tissues. When the tissue is injured by mechanical or chemical factors, some substances are released from the affected area, which produces series of reactions in the affected area:
      1. The chemical substances released from the damaged tissue such as histamine, serotonin leukotrienes, prostaglandins, and bradykinin cause vasodilatation. It results in very (rushing of blood) in the affected area
      2. From the blood, many leukocytes particularly’ neutrophils and monocytes infiltrate the info- area. The leukocytes play an important role m the defensive mechanism
      3. The vasodilator substances released in the affected area increase the permeability of the capillary membrane resulting in the oozing out of fluid from blood into interstitial space
      4. Coagulation occurs in the interstitial fluid because of fibrinogen and other proteins which are leaked out from blood
      5. Finally, edema occurs in that area which may be a nonpitting type because of hard clot formation.
    • Glucocorticoids prevent inflammatory changes in the injured or infected tissues by acting at all stages of inflammation.
    • Glucocorticoids cause the stabilization of the membrane of the lysosome. This inhibits the release of proteolytic enzymes responsible for inflammation
    • The release of substances like histamine and proteolytic enzymes from affected tissues is prevented
    • By the permissive action on catecholamines, glucocorticoids cause vasoconstriction and prevent a rush of blood to the injured area
    • Glucocorticoids inhibit the migration of leukocytes into the affected area
    • The permeability of capillaries decreases so that loss of fluid from plasma into the affected tissue is prevented
    • Glucocorticoids suppress T cells and other leukocytes so that, there is a reduction in the reactions of tissues which usually enhance the inflammatory process
    • In addition to preventing inflammatory reactions, if the inflammation has already started, glucocorticoids cause an early resolution of inflammation and rapid healing.
14. Anti-allergic Actions: Corticosteroids prevent the various reactions in allergic conditions as in the case of inflammation.
15. Immunosuppressive Effects
    • Glucocorticoids suppress the immune system of the body by decreasing the number of circulating T lymphocytes.
    • It is done by suppressing lymphoid tissues, i.e. lymph nodes and thymus and the proliferation of T cells. Gluco- is also prevent the release of interleukin-2 by T cells, hypersecretion, or excess use of glucosidases the immune reactions against all entering the body. It leads to severe sing death.
    • The immunological reactions, which are common -n transplantation, may cause rejection of the ranspianted tissues. Glucocorticoids are used to suppress the immunological reactions, because of their immunosuppressive action.

Glucocorticoids Mode Of Action: Glucocorticoids bind with receptors to form hormone- receptor complex which activates DNA to form mRNA. mRNA causes synthesis of enzymes, which alter the cell function.

Glucocorticoids Regulation Of Secretion: Anterior pituitary regulates glucocorticoid secretion by secreting adrenocorticotropic hormone (ACTH). ACTH secretion is regulated by the hypothalamus through corticotropin-releasing factor (CRF).

• Role of Anterior Pituitary – ACTH: Anterior pituitary controls the activities of adrenal cortex by secreting ACTH. ACTH is mainly concerned with the regulation of cortisol secretion. It plays only a minor role in the regulation of mineralocorticoid secretion.
  • Source: ACTH is secreted by the basophilic chromophilic cells of the anterior pituitary.
  • Chemistry plasma level and half-life: It is a single chained polypeptide with 39 amino acids. The daily output of this hormone is 10 ng and the concentration in plasma is 3 ng/dL. The half-life of ACTH is 10 minutes.
  • Synthesis: ACTH is synthesized from a protein called pre-pro-opio- melanocortin (POMC). Along with ACTH, the POMC gives rise to some more byproducts called β-lipotropin, γ-lipotropin, and β-endorphin. Two more byproducts namely, β-melanocyte stimulating hormone (β-MSH) and β-melanocyte stimulating hormone (MSH) are also secreted in animals. However, MSH activity is shown by ACTH and other byproducts from POMC in human beings.
  • Actions: ACTH is necessary for the structural integrity and the secretory activity of adrenal cortex. It has other functions also.
  • Actions of ACTH on adrenal cortex (Adrenal actions)
    1. Maintenance of structural integrity and vascularization of zona fasciculata and zona reticularis of adrena’ cortex. In hypophysectomy, these two layers in the adrenal cortex are atrophied
    2. Conversion of cholesterol into pregnenolone, which is the precursor of glucocorticoids. Thus, adrenocorticotropic hormone is responsible for synthesis of glucocorticoids
    3. Release of glucocorticoids
    4. Prolongation of glucocorticoid action on various cells.
  • Other (Nonadrenal) actions of ACTH
    1. Mobilization of fats from tissues
    2. Melanocyte stimulating effect. Because of its structural similarity with melanocyte-stimulating hormone, ACTH shows melanocyte stimulating effect. It causes darkening of skin by acting on melanophores which are the cutaneous pigment cells containing melanin.
  • Mode of action of ACTH: ACTH acts by the formation of cyclic AMP.
• Role of Hypothalamus
  • Hypothalamus also plays an important role in the regulation of cortisol secretion by controlling the ACTH secretion through corticotropin-releasing factor (CRF). It is also called corticotropin-releasing hormone. CRF reaches the anterior pituitary through the hypothalamic-hypophyseal portal vessels.
  • CRF stimulates the corticotropes of anterior pituitary and causes the synthesis and release of ACTH.
  • CRF secretion is induced by several factors such as emotion, stress, trauma, and circadian rhythm. CRF in turn, causes the release of ACTH, which induces glucocorticoid secretion.
  • Feedback Control: Cortisol regulates its own secretion through negative feedback control by inhibiting the release of CRF from the hypothalamus and ACTH from anterior pituitary.
    • Circadian rhythm of ACTH: ACTH secretion follows circadian rhythm, i.e. it varies in different periods of the day. The rate of secretion of both ACTH and CRF is high in the morning and low in the evening. Hypothalamus plays an important role in the circadian fluctuations of ACTH secretion.