EFFECTS OF ACTH AND ITS O-NITROPHENYL SULPHENYL DERIVATIVE ON ADRENOCORTICAL FUNCTION IN VIVO

Abstract

Both ACTH and NPS-ACTH [o-nitrophenyl sulphenyl-ACTH] in which the single tryptophan residue of the hormone is modified were able to stimulate adrenal corticosterone concentration to the same extent in hypophysectomized rats, although a higher dose of NPS-ACTH was required. ACTH stimulated adrenal cyclic[c]AMP levels 120-fold in hypophysectomized rats; NPS-ACTH caused a marginal increase. In the case of ACTH, low doses of the hormone capable of producing maximal stimulation of corticosterone synthesis did not produce any detectable change in cAMP concentration. The rates of secretion of corticosterone induced by ACTH and NPS-ACTH in vivo were the same. NPS-ACTH was 1.2% as potent as ACTH. The role of cAMP in adrenal repair was investigated by administering equipotent doses of ACTH or NPS-ACTH to hypophysectomized rats. In adult rats both failed to produce a significant increase in adrenal weight. Adrenal function (measured by responsiveness to exogenous ACTH in vitro) was restored by NPS-ACTH but not to the same degree as ACTH. In hypophysectomized weanling rats, ACTH produced a small but significant increase in adrenal weight but NPS-ACTH did not. An increase in adrenal cAMP possibly may not be obligatory for the stimulation of steroidogenesis by ACTH and some of the trophic actions of the hormone possibly may be mediated by cAMP.