Physiological Effects Of Glucocortioids

Of the naturally occurring steroids only cortisol, corticosterone, cortisone, and 11-dehydrocorticosterone have appreciable glucocorticoid activity. Cortisol, which is found in the highest concentration, accounts for most of this activity. About 75% of plasma cortisol is bound to cortisol binding globulin (CBG, an alpha globulin), 15% is bound to plasma albumin, and 10% is unbound (free), representing the physiologically active portion. CBG also has a high binding affinity for progesterone, deoxycorticosterone, and some synthetic analogs.

2.1. Anti-Inflammatory Effects

Glucocorticoids inhibit inflammatory and allergic reactions. They do this by stabilizing the lysosomal membranes, inhibiting the release of proteolytic enzymes, and by increasing capillary permeability. This in turn reduces dia-pedesis of leukocytes. Glucocorticoids also reduce the number of circulating lymphocytes, monocytes, eosinophils, and basophils. The decrease in the number of basophils accounts for the fall in blood histamine levels and the reduction of the allergic response. There is also an increase in the number of inflammatory cells (neutrophils) caused by a decrease in the migration from the capillaries and an accelerated release from bone marrow. Glucocorticoids also inhibit the ability of neutrophils to marginate to the vessel wall. In addition, they cause impairment of the lymph nodes, thymus, and spleen that directly leads to decreased antibody formation.

2.2. Antigrowth Effects

Large doses of cortisol have been shown to antagonize the effect of active vitamin D metabolites on the absorption of Ca2+ from the gut, inhibit mitosis of fibroblasts, and cause degradation of collagen. All of these effects can lead to osteoporosis, which is a reduction in bone mass per unit volume. Glucocorticoids can also delay wound healing because of the reduction of fibroblast proliferation. Connective tissue is reduced in quality and strength. In addition, chronic supra-physiologic doses of glucocorticoids will suppress growth secretion and inhibit somatic growth.

2.3. Vascular Effects

Cortisol in pharmacological doses will enhance the vasopressor action of catecholamines. Thus, corticosteroids have a role in maintenance of normal arterial systematic blood pressure and volume through their support of vascular responsiveness to vasoactive substances. Cortisol also enhances cat-echolamine synthesis via activation of the epinephrine-forming enzyme.

2.4. Other Effects

Glucocorticoids, unlike mineraldocorticoids, restore glomerular filtration rate (GFR) and renal plasma flow to normal following adrenalectomy. They also facilitate free-water excretion (clearance) and uric-acid excretion. Of Glucocorticoids have also been found to have psychoneural effects following chronic hyper- or hypo-cortisol secretion. In these cases patients may initially become euphoric and then psychotic, paranoid, and finally depressed. In addition, cortisol increases gastric flow and gastric secretion, while it decreases gastric mucosal-cell proliferation. The latter two effects can lead to peptic ulceration following chronic cortisol treatment.

2.5. Metabolic Effects

2.5.1. Carbohydrate Metabolism

Cortisol, the main glucocorticoid present in circulation, is a carbohydrate-sparing hormone exerting an anti-insulin effect, which can lead to hypogly-cemia and insulin-resistance. In addition, glucocorticoids maintain blood glucose and the glycogen content of the liver by promoting the conversion of amino acids to carbohydrates and the storage of carbohydrate as hepatic glycogen.

2.5.2. Protein Metabolism

The most important gluconeogenic substrates are amino acids that are derived from proteolysis in skeletal muscle. Cortisol enhances the release of amino acids from proteins in skeletal muscles and other extra hepatic tissues including the protein matrix of bone. The amino acids released are transported to the liver and then converted to glucose. This increased in glucose production via gluconeogenesis causes an increased urea production because of the conversion of amino-acid nitrogen to urea, accounting for the increased urinary nitrogen excretion. The proteolysis in skeletal muscle brings about a negative protein balance since the amino acids taken up by the liver that would have been used in the synthesis of new protein are instead used to form glucose or glycogen. This anabolic effect is an important exception to the overall protein catabolic effect of cortisol.

2.5.3. Fat Metabolism

Glucocorticoids enhance the lipolytic actions of other hormones, such as growth hormone, catecholamines, glucagon, and thyroid hormone. Gluco-corticoids also help in the mobilization of fatty acids from adipose tissues to the liver, where the metabolism of fatty acids inhibits glycolytic enzymes and promote gluconeogenesis. As a result of increased fatty acids oxidation, glucocorticoids may lead to increased ketosis, especially in patients with diabetes mellitus.

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Responses

  • gordon marshall
    What are vasopressors used for?
    8 years ago

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