Comparison of Effects of 6-Dehydro-16-Methylene-Hydrocortisone (Stc 407) and Dexamethasone on the Suppression of the Hypothalamo-Pituitary-Adrenal System

Abstract

The suppressive effects of 6-dehydro-16-methylene-hydrocortisone (STC 407) and dexamethasone on the hypothalamo-pituitary-adrenal system were evaluated in the rat. Four μg dexamethasone or 120 μg STC 407/100 g b. w. was injected ip daily into normal rats for 16 or 31 days. These doses were of approximately equivalent antiinflammatory potencies. Both steroids decreased equally plasma and adrenal corticosterone concentrations as well as adrenal weights. However, CRF activities of the hypothalamus and ACTH contents of the pituitary glands were significantly reduced by treatment with STC 407, but not with dexamethasone. This finding may endorse the successful treatment with STC 407 of Cushing's syndrome due to adrenal hyperplasia in which the fundamental derangement appears to consist of a disturbed regulatory function of the hypothalamus.

Review Article: Acth and Related Peptides

“…Many different types of physical and psychological stress cause ACTH release (Rees et al, 1971). The ACTH response is thought to be mediated by corticotrophin-releasing factor (Frohman, 1972) and inhibited by cortisol or synthetic glucocorticoids (Berson & Yalow, 1968;Fleischer et al, 1969;Berthold et al, 1970). Any interference with the synthesis of cortisol, and its negative feedback effect on ACTH release, will result in increased secretion.…”