Effects of β-Lipotropin, β-Endorphin, γ2-Melanotropin and Corticotropin on Steroid Production by Isolated Human Adrenocortical Cells

Abstract

Summary:Normal human adrenocortical cells (from multi-organ donors) were incubated with corticotropin (tetracosactide), highly purified human ß-lipotropin, synthetic human ß-lipotropin, y 2 -melanocyte stimulating hormone and ß-endorphin. Corticotropin stimulated cortisol, aldosterone and 18-hydroxycorticosterone production starting at " 12 -10" 11 mol/1 in normal adrenocortical cells. Purified human ß-lipotropin also stimulated steroidogenesis but 100 -lOOOfold higher concentrations of the peptide were needed. In contrast, synthetic human ß-lipotropin was without any effect on steroid production up to concentrations of 10~? mol/1. Synthetie ß-lipotropin (5 10~1 0 mol/1) did not significantly change the dose-response curve for corticotropin (10~1 3 mol/1-10~9 mol/1) versus the three steroids ineasured. y 2 -Melanotropin and ß-endorphin (10~6 mol/1) stimulated the secretion of cortisol, but not of aldosterone.Since synthetic human ß-lipotropin has no effect on human adrenocortical cells, the purified ß-lipotropin must be contaminated with traces of eorticotropin. Since pathologically elevated levels of proopipmelanocortin-derived peptides will rarely exceed plasma concentrations of 10~1 0 mol/1, our findings in vitro do not support a physiological or pathophysiological role of the peptides examined in the regulation of adrenal steroid secretion.

In vivo and in vitro Studies in a Patient with Cyclical Cushing’s Disease Showing Some Responsiveness to Bromocriptine

“…We speculate so because Lam berts et al [6] reported a higher adrenocortical respon siveness to ACTH in vitro in patients with Cushing's disease having macronodular adrenocortical hyperplasia than in those with diffuse hyperplasia. Second, it is also possible that in the present case various POMC-derived peptides implicated in the regulation of adrenocortical function [7][8][9][10][11] may have significantly affected cortisol secretion independently of or in concert with ACTH.…”