Cortisol and testosterone: inhibitory agents of the mineralocorticoid pathway. Is there a physiopathological meaning in adrenal tumors?
The authors incubated adrenal mitochondria to study the in vitro action of cortisol and testosterone on the transformation of corticosterone and 18-hydroxycorticosterone into aldosterone. The results show that cortisol at concentrations of 5 x 10(-6) and 10(-4) M inhibit the conversion of corticosterone into aldosterone by 23.6 to 90%; testosterone 5 x 10(-5) and 10(-4) M inhibit the reaction by 78.4 and 87.2%, respectively. The inhibition of the conversion of 18-hydroxycorticosterone into aldosterone is 12.5 to 91% by cortisol with concentrations ranging from 5 x 10(-7) to 5 x 10(-5) M and testosterone 5 x 10(-5) and 10(-4) M inhibits the reaction by 87.3 and 91%, respectively. Aldosterone (10(-8) and 10(-6) M) does not inhibit aldosterone biosynthesis from corticosterone or 18-hydroxycorticosterone. It thus appears that cortisol and testosterone have an effect on the aldosterone biosynthesis pathways in mitochondria. This action may be located at the binding site of the cytochrome P450 11 beta, which catalyzes all hydroxylation steps in the mineralocorticoid biosynthesis pathway. Because cortisol and testosterone may interfere with aldosterone biosynthesis, and since functional zonation is expected in adrenal carcinomas, the presence of these steroids in substantial amounts could explain the very low plasma aldosterone level usually observed, in adrenal carcinomas studied in our laboratory.
Emeric-Blanchouin
N
N
Service de Biochimie Médicale, Faculté de Médecine Pitié-Salpétrière, Paris, France.
Zenatti
M
M
Vonarx
V
V
Schaison
G
G
Aupetit-Faisant
B
B
D000310:Adrenal Gland Neoplasms / Q000503:physiopathology*; D000311:Adrenal Glands / Q000378:metabolism*; D000450:Aldosterone / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D004372:Ducks; D006854:Hydrocortisone / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology*
D008901:Mineralocorticoids; D013739:Testosterone; D000450:Aldosterone; D003345:Corticosterone; D006854:Hydrocortisone