Glucocorticoids In Humans Research Articles

Inhibition of eicosanoid biosynthesis by glucocorticoids in humans.

Therapeutic doses of glucocorticoids are thought to inhibit prostaglandin and leukotriene formation in humans. Several studies in animals, however, have failed to demonstrate modulation of eicosanoid biosynthesis by steroids in vivo. We administered prednisone (60 mg/day) to eight healthy volunteers and measured eicosanoid formation by a variety of cell types in vivo and ex vivo, using sensitive and specific physicochemical assays. We found that the in vivo course of prednisone failed to inhibit the synthesis of thromboxane A2, prostaglandin I2 (prostacyclin), prostaglandin E2, and leukotriene E4 in vivo and of leukotriene B4 ex vivo. Biosynthesis of leukotriene B4, thromboxane B2, and prostaglandins F2 and E2 by macrophage-rich bronchoalveolar lavage cells was strongly suppressed. These findings indicate that therapeutic regimens of glucocorticoids suppress eicosanoid biosynthesis in human macrophages but not in a number of other cell types with steroid receptors, the capacity for eicosanoid formation, and lipocortin-like material.

RU 486 inhibits peripheral effects of glucocorticoids in humans.

RU 486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-(prop-1-ynyl)estra-4,9-dien-3-one] is a synthetic steroid receptor antagonist. To evaluate the peripheral antiglucocorticoid action of this compound, we investigated its ability to antagonize cutaneous steroid-induced vasoconstriction. This phenomenon, produced by three different topical steroids in six normal men, was consistently and significantly attenuated or abolished by oral administration of 6 mg/kg RU 486. This demonstration of a peripheral action of RU 486 is important in relation to the potential therapeutic use of this well tolerated drug in states of hypercortisolism. It also indicates that the cutaneous vasoconstrictor effects of topical steroids are mediated by occupancy of glucocorticoid receptors.

Toxic reactions and side effects of glucocorticoids in man

The toxic reactions and side effects of glucocorticoids in humans are discussed. The effects reviewed include metabolic (muscle and skin, carbohydrates and lipids), cardiovascular, cellular, immunologic, skeletal and growth, gastrointestinal, nervous system, ocular, and hypothalmic-pituitary-adrenal.

Tachyphylaxis to Topically Applied Steroids

• Acute tolerance to the vasoconstrictive effect of topically applied glucocorticoids in humans has recently been described. Similar acute tolerance to the antiproliferative properties of topically applied steroids in proliferating and normal hairless mouse epidermis is now shown to occur. Thus, at first, topically applied steroids cause profound inhibition of DNA synthesis and mitosis in the epidermis, but with continued treatment, DNA synthesis and mitosis recover and the tissue becomes insensitive to further stimulation. This suggests that there is an optimum approach to therapy with topically applied steroids that might reduce the incidence of side effects and improve therapeutic efficacy. (<i>Arch Dermatol</i>112:1245-1248, 1976)

Tachyphylaxis to topically applied steroids.

Acute tolerance to the vasoconstrictive effect of topically applied glucocorticoids in humans has recently been described. Similar acute tolerance to the antiproliferative properties of topically applied steroids in proliferating and normal hairless mouse epidermis is now shown to occur. Thus, at first, topically applied steroids cause profound inhibition of DNA synthesis and mitosis in the epidermis, but with continued treatment, DNA synthesis and mitosis recover and the tissue becomes insensitive to further stimulation. This suggests that there is an optimum approach to therapy with topically applied steroids that might reduce the incidence of side effects and improve therapeutic efficacy.