EFFECTS OF HYPOPHYSECTOMY WITH OR WITHOUT ACTH MAINTENANCE THERAPY ON THE FINAL STEPS OF ALDOSTERONE BIOSYNTHESIS IN THE RAT

Abstract

ABSTRACT The effects of hypophysectomy, low-dose ACTH administration or both on aldosterone biosynthesis by incubated adrenal tissue were studied in rats during different dietary regimens. Six days after hypophysectomy without any replacement therapy, the capsular adrenals of rats receiving a complete diet converted tritiated corticosterone to aldosterone and 18-hydroxycorticosterone at a normal and at a moderately increased rate, respectively, and produced normal amounts of aldosterone from endogenous precursors. Hypophysectomy, with ACTH maintenance therapy, resulted in significant decreases in these parameters. In rats kept on a sodium-deficient diet, hypophysectomy alone did not alter the conversion rates, but led to a decreased output of endogenous aldosterone. ACTH treatment of intact as well as of hypophysectomized sodium-restricted animals was followed by a decreased incorporation of tritiated corticosterone into aldosterone and 18-hydroxycorticosterone. In rats kept on a potassium-deficient diet, hypophysectomy induced an 800 % increase in the capsular adrenal conversion of added corticosterone to aldosterone and 18-hydroxycorticosterone; this was partially prevented by ACTH treatment. Hypophysectomy with or without ACTH treatment did not impair restoration to the normal of the apparent capsular adrenal 18-hydroxylase activity in response to resumed potassium intake by potassium-restricted rats. These results indicate that neither the maintenance nor the induction of an increased activity of the enzymes involved in the final steps of aldosterone biosynthesis due to sodium restriction or to an increased potassium intake, depend on a functioning pituitary gland. On the other hand, even small doses of exogenous ACTH, which are just sufficient for the maintenance of a normal adrenal weight in hypophysectomized animals, can cause significant decreases in the activity of these enzymes.