TIn vitro study of frog ( Rana ridbunda Pallas) interrenal function by use of a simplified perifusion system IV. Influence of metyrapone and aminoglutethimide upon aldosterone production

Abstract

A perifusion system technique has been used to compare the effects of metyrapone (SU-4885; Ciba) and aminoglutethimide, two compounds which are known to inhibit corticosteroid biosynthesis in mammal adrenal glands, upon aldosterone output by frog interrenal tissue. Rana ridibunda adrenal fragments were continuously perifused for 13 hr with amphibian culture medium. Fractions were set apart every 5 min and aldosterone levels were measured by means of a specific and sensitive radioimmunoassay method. For doses ranging from 1 × 10 −6 to 1 × 10 −3 M, metyrapone induced a decrease in aldosterone secretion rate. The infusion of three equimolar doses (1 × 10 −5 M)_of metyrapone during three consecutive periods of 1 hr or during various times (30, 60, 150 min) within the same experiment made it possible to study the kinetics of the response of the glands. The lag period (10 min), the amplitude of the inhibition (75%), and the duration of the inhibitory effect after withdrawal of metyrapone (50 min) were almost uniform, whatever the duration of the infusion. Similar patterns were obtained using aminoglutethimide, although much higher doses (up to 100-fold) were required to inhibit aldosterone production. These results demonstrate that both metyrapone and aminoglutethimide are potent inhibitors of mineralocorticoids output in amphibia. Conversely, they suggest that a single injection of each inhibitor, in vivo, would only induce a transient and light diminution in corticosteroid secretion.