J. J. Chart

Pharmacologic alteration of steroid hormone functions

A large number of compounds can modify the function, synthesis, or metabolism of steroid hormones. These are not necessarily otherwise related chemically or pharmacologically. The drugs used as examples in this review were selected to show the wide variety of potential sites and modes of action. While many compounds have been shown to interfere with one or another step in the biosynthesis of corticosteroids, the number of known substances having any profound effect on gonadal steroidogenesis is surprisingly few. On the other hand, many more compounds are known either to mimic or modify the end‐organ response to gonadal than to adrenal steroids. The field of endocrine pharmacology is being rapidly widened as systematic searches are now being made for drugs which affect endocrine function either as a primary or incidental action.

Sulfonamide compounds with high diuretic activity

Abstract Several related compounds are more active than chlorothiazide in enhancing water, sodium, and, generally, potassium excretion in rats. Of these, hydrochlorothiazide had from seven to twenty-one times the potency of chlorothiazide, depending upon the parameter measured and conditions of test. After administration of the drug, an increased rate of sodium excretion preceded marked change in water excretion. Hydrochlorothiazide modified renal response to vasopressin, reserpine, syrosingopine, aldosterone, DCA, and prednisolone and to adrenalectomy. It did not modify the hypertensive response to hydrocortisone but did inhibit blood pressure rise in adrenal regeneration hypertension when given chronically, but not acutely.

Effect of New Adrenal Steroids on Electrolyte and Water Excretion

Summary The effects of prednisone, prednisolone, hydrocortisone and desoxycorticosterone on excretion of water, sodium, and potassium, were compared in water-loaded adrenalectomized rats. All steroids stimulated water diuresis and potassium excretion. Hydrocortisone, prednisone and prednisolone were equi-potent; desoxycorticosterone was weaker. Hydrocortisone, prednisone and prednisolone stimulated sodium excretion at all doses having any effect and were again approximately equipotent. Desoxycorticosterone had the opposite effect and caused sodium retention. The relative inability of the Δ1-steroids to cause sodium retention under conditions of clinical use is, therefore, not associated with any comparable inability to cause natriuresis under appropriate circumstances.

Interaction of methandrostenolone and adrenocortical hormones.

Summary The anabolic steroid methan-drostenolone partially antagonized the growth inhibiting effects of glucocorticoids in rats and also, depending on the type of experiment, augmented or added to the anti-inflammatory activity of these steroids. Similar activity was found with methyltestosterone and testosterone, whereas norethandrolone and progesterone were inactive. The action of methandrostenolone was independent of the adrenal. Methandrostenolone itself showed no other signs of glucocorticoid-like activity. The authors wish to express their appreciation to Dr. Robert Gaunt for advice and encouragement and to Mrs. Hanna Sylwestrowicz for statistical evaluation. Thanks are due also to Nancy Howie, Margot Stein, Patricia Reilly and Viola Dube for technical assistance.

Effect of an Adrenal 17α-Hydroxylase Inhibitor on Gonad Function

Summary 7-Chloro-3,4-dihydro-2-(3-pyridyl)-1 (2H)-napthalenone (Su-10603), a compound known to inhibit particularly 17α-hydroxylation in the adrenal of the dog, was studied for its effects on gonad and adrenal function in rats. Administration to immature animals for 30 days (100-400 mg/kg/day) inhibited growth of seminal vesicles, ventral prostates, levatores ani and uteri without other obvious effects. It was similarly active in adrenalectomized rats. These results are consistent with previous demonstrations that the drug interferes with testosterone synthesis in vitro. The Su-10603 also inhibited the response of immature males but not females to chorionic gonadotropin as judged by weights of sex accessories. It interfered with the normal processes of pregnancy by means as yet undetermined. Unlike the situation in the dog, it was without effect on adrenal morphology or the corticosterone secretion rate in rats.