Faculty Collaboration Database

Effects of angiotensin, prostaglandin E2 and indomethacin on the early and late steps of aldosterone biosynthesis in isolated adrenal cells. J Steroid Biochem 1986 Apr;24(4):865-70

Date

04/01/1986

Pubmed ID

3458007

DOI

10.1016/0022-4731(86)90447-4

Scopus ID

2-s2.0-0022627460 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

The involvement of prostaglandins in the regulation of aldosterone biosynthesis was investigated in isolated adrenal glomerulosa cells. Cells were treated with cyanoketone to inhibit the 3 beta-hydroxy-steroid dehydrogenase and isolate the early step of aldosterone synthesis and the late step. Angiotensin II and PGE2 stimulated the synthesis of aldosterone in a concentration-related manner. The stimulation by both compounds was inhibited by indomethacin, a prostaglandin synthesis inhibitor. Indomethacin also inhibited arachidonic acid-stimulation of 6-keto PGF1 alpha synthesis, whereas cyanoketone was without effect. Both angiotensin II and PGE2 stimulated the synthesis of pregnenolone (the early step) in a concentration-related manner. At higher concentrations, angiotensin II also stimulated the conversion of [3H]corticosterone to [3H]aldosterone (the late step). PGE2 did not alter the late step significantly. Indomethacin had no effect on either biosynthetic step when added alone. However, it inhibited the angiotensin- and PGE2-stimulated pregnenolone synthesis by 41 and 59%, respectively (P less than 0.05). Indomethacin did not alter angiotensin stimulation of the conversion of corticosterone to aldosterone. These findings indicate that PGE2 increases the synthesis of aldosterone by stimulating the conversion of cholesterol to pregnenolone. Indomethacin inhibits angiotensin II- and PGE2-induced steroidogenesis at the same early biosynthetic step. These findings suggest that indomethacin may act by a mechanism other than a reduction in the concentration of prostaglandins.

Author List

Campbell WB, Brady MT, Gomez-Sanchez CE

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenal Cortex
Aldosterone
Angiotensin II
Animals
Corticosterone
Dinoprostone
In Vitro Techniques
Indomethacin
Kinetics
Male
Pregnenolone
Prostaglandins E
Rats
Rats, Inbred Strains