19-Acetylenic-deoxycorticosterone inhibits 19-hydroxylase and 11 beta-hydroxylase activities in dispersed bovine zona fasciculata cells.
19-Acetylenic-deoxycorticosterone (19-A-DOC) is believed to be a competitive irreversible inhibitor of the synthesis of 19-nor-deoxycorticosterone (19-nor-DOC), a potent mineralocorticoid implicated in some forms of human and animal hypertension. It has been shown to inactivate 11 beta/19-hydroxylase in hamster adrenal mitochondria. Dispersed bovine zona fasciculata cells were incubated for one hour with 1.5 x 10(-8) M ACTH and 0, 1, 10, or 100 microM 19-A-DOC and tritiated deoxycorticosterone (DOC) substrate. Steroids were separated using two sequential thin-layer chromatography systems and their tritium content was counted and corrected for recovery. The 19-A-DOC decreased synthesis of 19-hydroxydeoxycorticosterone, the precursor of 19-nor-DOC. The inhibitor also impaired 11-hydroxylation of DOC to form corticosterone. The data suggest that 19-A-DOC is an effective inhibitor of 11 beta/19-hydroxylase activity in dispersed bovine adrenal cells.
Delaney
M L
ML
Section of Endocrinology and Metabolism, Evans Medical Foundation, University Hospital, Boston University Medical Center, Massachusetts 02118, USA.
Melby
J C
JC
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors*; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*; D014316:Tritium; D015383:Zona Fasciculata / Q000201:enzymology*
D014316:Tritium; C076838:19-acetylenic-deoxycorticosterone; D003900:Desoxycorticosterone; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; C027110:steroid 19-hydroxylase; D013252:Steroid 11-beta-Hydroxylase