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 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 (Ki = 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
Matkovic, Laura,Gomez-Sanchez, Celso E.,Lantos, Carlos P.,Cozza, Eduardo N.
p. 447 - 452
(2007/10/02)
Differences between adrenal adenoma causing primary aldosteronism and other adrenal tissues in the incorporation of labeled steroid precursors into their products
The incorporation and conversion of several labeled steroid precursors into their products were examined in slices of adrenal tissue from two patients with primary aldosteronism and compared with that in 'normal' adrenal tissue and adrenal tissues from a patient with Cushing's syndrome. The products of the incorporation were separated by Sephadex LH-20 column chromatography. The major products of conversion in the adenomatous tissue of primary aldosteronism were 18-hydroxycorticosterone and lesser amounts of aldosterone. Smaller amounts of 18-hydroxycorticosterone were isolated from all other adrenal tissues studied. No aldosterone could be recovered after incubating any of the adrenal tissue studied with labeled 18-hydroxy-11-deoxycorticosterone or 18-hydroxycorticosterone as precursor steroid. These in vitro results seem to suggest that there is increased 18-hydroxylation in the adenoma of primary aldosteronism compared with other tissues and that relatively more 18-hydroxycorticosterone is produced in such tissue than aldosterone.
Usa,Ganguly,Weinberger
p. 531 - 545
(2007/10/02)
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