Met-Enkephalin Inhibits Mineralocorticoid Production in Isolated Human Aldosteronoma Cells

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Abstract
In vitro application of the morphinomimetic metenkephalin resulted in inhibition of mineralocorticoid production by aldosterone-producing adenomas. Aldosterone, deoxycorticosterone, and corticosterone production by adrenocortical cells isolated from aldosteronomas has been studied under basal conditions and after stimulation with ACTH-(l-24). The blocking effect of met-enkephalin on the rate of aldosterone, deoxycorticosterone, and corticosterone release was significant at a concentration as low as 10-11 u (P μ 0.001, P μ 0.01, and P μ 0.001, respectively). Dose-dependent inhibition of steroid biosynthesis became more apparent with increasing amounts of met-enkephalin in the incubation medium (10-11-10-5 M); at a concentration of 10-5 M, met-enkephalin decreased the production of aldosterone by 45%, that of deoxycorticosterone by 51%, and that of corticosterone by 44%. Increased steroid biosynthesis stimulated by ACTH-(l-24) was also significantly blocked by met-enkephalin. In a concentration of 10-5 M, met-enkephalin produced significant decreases in aldosterone (P μ 0.001), deoxycorticosterone (P μ 0.05), and corticosterone (P μ 0.001) production compared to the peak values obtained after stimulation with 0.85 x 10-10 M ACTH-(1- 24). These data allow us to conclude that the inhibitory effect of met-enkephalin on mineralocorticoid production exerted at the level of the adrenals might be complementary to the factor(s) thought to be involved in the regulation of adrenal steroid production, playing a role similar to that of the biogenic amines originating in the adrenal medulla and regulating the adrenal cortex by a peripheral neurohumoral paracrine mechanism.