Inhibition of aldosterone formation by cortisol in rat adrenal mitochondria.
In this work we confirm by a metabolic method the existence of at least two enzymes with 11 beta- 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 (Ki = 2.5 +/- 0.5 microM); and c) ALDO production from 18-OHDOC. These results suggest the existence of two categories of enzymes with both 11 beta- and 18-hydroxylase activities, one comprising those that catalyze the conversions of DOC to B and 18-OHDOC (F-insensitive reactions [FIS]) 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 [FS]). The cloned enzymes CYP11B1 and CYP11B2 would pertain respectively to the FIS and FS categories.
Matković
L
L
Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Gomez-Sanchez
C E
CE
Lantos
C P
CP
Cozza
E N
EN
D015069:18-Hydroxycorticosterone / Q000378:metabolism; D000311:Adrenal Glands / Q000648:ultrastructure*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D008928:Mitochondria / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D051381:Rats
D000451:Mineralocorticoid Receptor Antagonists; C042509:18-hydroxydeoxycorticosterone; D003900:Desoxycorticosterone; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D006899:Mixed Function Oxygenases; D006854:Hydrocortisone