Inhibition of aldosterone formation by cortisol in rat adrenal mitochondria

Article abstract of DOI:10.1016/0039-128X(94)00064-J

In this work we confirm by a metabolic method the existence of at least two enzymes with 11β- and 18-hydroxylase activities in rat adrenal mitochondria.The method was based on the ability of cortisol (F), a foreign alternative substrate, to inhibit competitively metabolite productions from various precursors.F inhibited a) aldosterone (ALDO) production from 11-deoxycorticosterone (DOC) without affecting the yields of corticosterone (B) and 18-hydroxy-11-deoxycorticosterone (18-OHDOC); b) 18-hydroxycorticosterone and aldosterone productions from B (K_i = 2.5 +/- 0.5 μM); and c) ALDO production from 18-OHDOC.These results suggest the existence of two categories of enzymes with both 11β- and 18-hydroxylase activities, one comprising those that catalyze the conversions of DOC to B and 18-OHDOC (F-insensitive reactions ) and the other one comprising the enzymes involved in the conversions of B to 18-OHB and ALDO and that of 18-OHDOC to ALDO (F-sensitive reactions ).The cloned enzymes CYP11B1 and CYP11B2 would pertain respectively to the FIS and FS categories. - Keywords: aldosterone; adrenal; cytochrome P450; 11β,18-hydroxylases; steroidogenesis; Cortisol