INHIBITION OF ALDOSTERONE FORMATION BY CORTISOL IN RAT ADRENAL MITOCHONDRIA

In this work we confirm by a metabolic method the existence of at leas t two enzymes with 11 beta- and 18-hydroxylase activities in rat adren al mitochondria. The method was based on the ability of cortisol (F), a foreign alternative substrate, to inhibit competitively metabolite p roductions from various precursors. F inhibited a) aldosterone (ALDO) production from 11-deoxycorticosterone (DOG) without affecting the yie lds of corticosterone (B) and 18-hydroxy-11-deoxycorticosterone (18-OH DOC); b) 18-hydroxycorticosterone and aldosterone productions from B ( K-i = 2.5 +/- 0.5 mu M); and c) ALDO production from 18-OHDOC. These r esults suggest the existence of two categories of enzymes with both 11 beta- and 18-hydroxylase activities, one comprising those that cataly ze the conversions of DOC to B and 18-OHDOC (F-insensitive reactions [ FIS]) and the other one comprising the enzymes involved in the convers ions of B to 18-OHB and ALDO and that of 18-OHDOC to ALDO (F-sensitive reactions [FS]). The cloned enzymes CYP11B1 and CYP11B2 would pertain respectively to the FIS and FS categories.