Met-enkephalin inhibits mineralocorticoid production in isolated human aldosteronoma cells.
In vitro application of the morphinomimetic met-enkephalin 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-(1-24). 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) M (P less than 0.001, P less than 0.01, and P less than 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-(1-24) was also significantly blocked by met-enkephalin. In a concentration of 10(-5) M, met-enkephalin produced significant decreases in aldosterone (P less than 0.001), deoxycorticosterone (P less than 0.05), and corticosterone (P less than 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.
D000236:Adenoma / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis*; D003345:Corticosterone / Q000096:biosynthesis; D003366:Cosyntropin / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine; D004745:Enkephalins / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D066298:In Vitro Techniques; D008901:Mineralocorticoids / Q000096:biosynthesis*
D004723:Endorphins; D004745:Enkephalins; D008901:Mineralocorticoids; D003366:Cosyntropin; D003900:Desoxycorticosterone; D000450:Aldosterone; D004744:Enkephalin, Methionine; D003345:Corticosterone; D006854:Hydrocortisone