Endothelin stimulates steroid secretion by frog adrenal gland in vitro: evidence for the involvement of prostaglandins and extracellular calcium in the mechanism of actin of endothelin.
Endothelin (ET-1) is a pleiotropic regulatory peptide which exerts multiple endocrine actions on the cardiovascular system. In the present study, we have investigated the possible role of ET-1 in the regulation of adrenocortical cells using perifused frog interrenal (adrenal) slices. Graded doses of ET-1 from 10(-11)-10(-9) M stimulated both corticosterone and aldosterone production in a dose-dependent manner. Repeated 20-min pulses of ET-1 (10(-9) M), given at the frequency of one pulse per 90 min, resulted in a marked reduction of the secretory response after the second pulse. Prolonged administration (3 h) of ET-1 induced a rapid increase in corticosterone and aldosterone output, followed by a gradual decline of corticosteroid secretion. Perifusion of frog adrenal tissue with ET-1 (10(-9) M) caused a significant increase in the release of prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha, the stable metabolite of the prostacyclin PGI2. The enhancement of PG biosynthesis preceded by 10 min the peak of corticosteroids. When repeated pulses of ET-1 were administered, a significant diminution of the production of PGE2 and 6-keto-PGF1 alpha was observed after the second pulse. The cyclooxygenase inhibitor indomethacin (5 microM) totally suppressed the stimulatory effect of ET-1 on corticosterone and aldosterone secretion; in contrast, indomethacin did not affect ACTH-evoked corticosteroid secretion. Perifusion of adrenal slices with a calcium-free solution or addition of cobalt (4 mM) induced total inhibition of the stimulatory effect of ET-1. These results demonstrate that ET-1 is a potent stimulator of corticosterone and aldosterone secretion from frog adrenal gland in vitro. Our data show that repeated or prolonged administration of ET-1 induces a rapid desensitization phenomenon. The data also indicate that ET-1-evoked corticosteroid secretion is mediated by an increase in PG biosynthesis and requires the presence of extracellular calcium.
Delarue
C
C
Groupe de Recherche en Endocrinologie Moléculaire, CNRS URA 650, Unité Affiliée l'INSERM, Université de Rouen, Mont Saint Aignan.
Delton
I
I
Fiorini
F
F
Homo-Delarche
F
F
Fasolo
A
A
Braquet
P
P
Vaudry
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D003345:Corticosterone / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D016232:Endothelins; D004730:Endothelium, Vascular; D011464:Epoprostenol / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011895:Rana ridibunda
D000305:Adrenal Cortex Hormones; D002121:Calcium Channel Blockers; D016232:Endothelins; D010455:Peptides; D011453:Prostaglandins; D003035:Cobalt; D000450:Aldosterone; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D015232:Dinoprostone; D002118:Calcium; D003345:Corticosterone; D007213:Indomethacin