Glucocorticoids

Cortisol, corticosterone, cortisone and 11‑dehydrocorticoster­one are the naturally occurring adrenal cortical steroids or Glucocorticoids.

The effect of glucocorticoids on carbohydrate metabolism is “permissive” i.e., their presence is required for the gluconeogenic and glycogenolytic actions of glucagon and epinephrine, respective­ly.

Cortisol

Gluco­corticoids have primary effect on carbohydrate metabolism-

1. Hypoglyce­mia is a potent stimulus for cortisol release to maintain normal plasma glucose level during fasting.
2. Cortisol is very potent and 95% of all glucocorticoid activity is provided by cortisol. Corticosterone provides 4% of all glucocorticoid activity.
3. Prednisolone, a synthetic corticosteroid is 4 times more powerful anti-inflammatory than cortisol. Dexamethasone, another synthetic corticoid is 30 times more powerful anti-inflammatory than cortisol.

Cortisol is a catabolic and diabetogenic hormone. It enhances the mobilization of amino acids from the muscle, amino acids uptake by the hepatic cells for hepatic gluconeogenesis, glycogenolysis and also the conversion of pyruvate to glycogen. The net result is an increase in hepatic glycogen and an increase in blood glucose.

Cortisol enhances the activities of phosphoenol pyruvate carbox­ykinase and hence the gluconeogenesis.

In pregnant animals it is important for the transport of glucose across the placenta.

Glucocorticoids and insulin have simi­lar effects on liver glycogen metabolism .

Cortisol stimulates in­creased liver glycogen deposition by inhibiting phosphorylase and stimulating glycogen synthase. However their effects on peripheral utilization of glucose are different.

Glucocorticoids inhibit glucose uptake and metabolism particularly in muscles and adipose cells which is referred as anti-insulin effect.

Glucocorticoids have direct effect on adipose tissue where it increases therate of lipolysis, thus plasma free fatty acids. It also potentiates the lipolytic actions of GH and epinephrine during fasting. It moderately enhances the utilization of fatty acids for energy. Glucocorticoids increase fat absorption and stimulate gas­tric acid and pepsin secretions. Cortisol also increases appetite.

The corticoids redistrib­ute body fat i.e. fat is lost from limbs and accumulated in head and trunk giving a pot belly appearance. In humans it gives a moon face appearance.

Extrahepatic protein synthesis is inhibited by glucocorticoids,

Protein catabolism is enhanced with an accompanying release of amino acids to support hepatic gluconeogenesis. Entry of amino acids into extrahepatic cells is inhibited. The mobilization and incorporation of amino acids into glycogen results in an increased urinary excretion of nitrogen and causes negative nitrogen balance that is accompa­nied by muscle wasting and reduced protein stores.

Liver proteins and plasma proteins are increased contrary to protein depletion in other cells.

Cortisol decreases the synthesis of 1, 25 DHCC and blocks calcium absorption from GI tract, thus increases bone resorption and decrease bone formation.

Hyperactivity of cortisol depresses the development of cartilage and the formation of bone interrupting the growth. Cortisol inhibits secretion of GH from the adenohypophysis. Cortisol inhibits the synthesis of collagen and causes thinning of the skin and walls of capillaries.

The diurnal increase in cortisol level in early morning (6.00 to 8.00 A.M.) is essential for normal arousal and initiation of day time activi­ties. An excess of cortisol interferes with sleep.

Glucocorticoids stimulates glomerular filtration rate and inhibit vasopressin activity at the level of distal tubule, thus play a role in water diuresis i.e., enhancement of water excre­tion.

Clinical effects of glucocorticoids

Glucocorticoids have valuable clinical effects particularly concerning inhibition of inflammatory response including the prevention of capillary dilatation, extravasation of fluid into tissue spaces, leukocyte migration, and fibrin deposition and connective tissue synthesis.

Cortisol causes reduction in circulating lymphocytes, eosinophils and basophils by causing lysis of these cells and also phagocytosis by WBCs but produces neutrophilia.

Glucocorticoids suppress immune response by T lymphocytes and also reduce the antibody production.

Glucocorticoids inhibit the synthesis of inflammatory mediating compounds such as prostaglandins, thromboxanes and leukotri­enes that arise as a result of arachidonic acid metabolism of injured cells by stabilizing the lysosomal membrane.

Cortisol inhibits the release of proteolytic enzymes and hyaluronidase from lysosome.

Glucocorti­coids are used to inhibit allergic reaction through its inhibitory action on the release of histamine from the granules of mast cells. Hence cortisol is useful in preventing death during allergy or anaphylaxis.

Prolonged administration of cortisol inhibits proliferation of fibro­blasts and synthesis and deposition of collagen fibrils and prevents normal wound healing after injury.

Cortisol facilitates in-utero maturation of the GI tract, lung, CNS, retina and skin. It stimulates increased synthesis of surfactant and permits satisfactory breathing immediately after birth. Cortisol facilitates the enzymatic actions of the intestinal mucosa and this permit the new born to digest the di-saccharides present in the milk.

In both males and females excess of glucocorticoids inhibit LH release, enhances the ability of the sex steroids to suppress gonadotropin secretions through negative feedback mechanism, thus delays the onset of puberty.

Cortisol from the fetal adrenal cortex acts upon the placenta to reduce progesterone and increase estrogen secretion both of which promotes the synthesis and release of PGF2α and uterine con­tractions are stimulated to induce labor.

Regulation of Glucocorticoids

Cortisol level rises in the early morning and declines in the afternoon and evening exhibiting a diurnal rhythm. The secretion of the glucocorticoids by zona reticularis is regulated by ACTH.

A negative feedback system exists whereby glucocorti­coids inhibit the release of CRH from the hypothalamus to decrease ACTH secretion by the pituitary. Cortisol has more potent negative feedback effect than corticosterone.

Another factor that can modify the negative feed back control of glucocorticoids is stress, which stimulates the secretion of glucocorticoids to several folds. ACTH administration depletes the zona fasciculata of cholesterol and vitamin C contents.

The adrenal cortical hormones are involved in the animal’s adaptation to adverse stress known as general adaptation syndrome or fight or flight response.

Failure of adrenal cortex to produce cortical hor­mones lead to a condition called Addison’s disease in human beings, dogs, cats and horses.

Hypersecretion of cortisol causes Cushing’s syndrome where fat is mobilized from lower part of the body and deposited in thoracic, abdominal regions and face (moon face). Other clinical signs include polyurea, polyphagia, hirsutism, skin pigmentation, poor wound healing and thin skin.