Endothelin enhances adrenocorticotropin-stimulated aldosterone release from cultured bovine adrenal cells.
Endothelin (ET) is an endothelial cell-derived peptide with profound hemodynamic effects. We investigated the effects of ET on steroid release from bovine adrenal cortical cells. ET-1 (10(-11)-10(-6) M) did not alter basal aldosterone release from adrenal glomerulosa cells. However, both angiotensin-II (AII)- and ACTH-stimulated aldosterone release from these cells. ET-1 enhanced ACTH-stimulated aldosterone release over a range of concentrations. This enhancement was observed at a threshold of 0.1 nM ET-1. Similar responses were observed in incubations of 1- and 2-h duration. In contrast, AII-stimulated aldosterone release was not altered by ET-1. ET-1 also enhanced aldosterone release in cells stimulated with 8-bromo-cAMP. All increased cytoplasmic Ca2+ concentrations in fura-2-loaded cells; however, ET-1 alone or with ACTH had no effect. In addition, chronic treatment of cells with ACTH for 2 days caused an enhanced release of aldosterone in cells acutely treated with ET-1 compared to cells not acutely treated (62% over chronic ACTH control; P less than 0.05). However, chronic treatment of ET-1 did not alter aldosterone secretion in the acute incubation compared to that in chronic controls. Thus, both acute and chronic exposures to ACTH sensitize glomerulosa cells to stimulation by ET-1. ET-1 did not alter basal or ACTH-stimulated cortisol release from adrenal fasciculata cells. Thus, the actions of ET-1 appear to be specific for glomerulosa cells. These data indicate that ET may exert a direct effect on adrenal glomerulosa cells to enhance ACTH-stimulated aldosterone release.
Rosolowsky
L J
LJ
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
Campbell
W B
WB
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D006854:Hydrocortisone / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*
D016232:Endothelins; D010455:Peptides; D000804:Angiotensin II; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D002118:Calcium; D006854:Hydrocortisone