Aldosterone synthase activity in the Y-1 adrenal cell line.
The Y-1 adrenal cell line was shown to produce 20 alpha-dihydroaldosterone from deoxycorticosterone. This compound was identified by GC-MS by comparison with the previously synthesized reference compound. Two other 18-hydroxylated metabolites were identified as 11 beta,18-dihydroxy-20 alpha-dihydroprogesterone from endogenous cholesterol and 18-hydroxy-20 alpha-dihydro-11-dehydrocorticosterone from DOC. The conditions necessary for the synthesis of these compounds are culturing in 20% serum-supplemented medium and repeated incubations with the substrate. The production of 11 beta-hydroxylated steroids and that of 18-oxygenated steroids is stimulated differently by ACTH and angiotensin II suggesting the expression of two different enzymes, cytochrome P-450(11)beta and cytochrome P-450aldo. The Y-1 cell line can secrete either 11 beta-hydroxylated steroids characteristic of the glucocorticoid pathway or 18-oxygenated steroids characteristic of the mineralocorticoid pathway, which in vivo are generally produced in two different zones of the adrenal cortex. This cell line should be an interesting model for the study of the molecular mechanisms regulating the expression of these two enzymes involved in the final steps of the steroidogenic pathways.
Es-souni Routhier
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M
Laboratoire de Biochimie, Faculté des Sciences, Université de Bourgogne, Dijon, France.
Bournot
P
P
Ramirez
L C
LC
D000302:Adrenal Cortex / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005938:Glucocorticoids / Q000378:metabolism; D051379:Mice; D008901:Mineralocorticoids / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics / Q000378:metabolism*
D005938:Glucocorticoids; D008901:Mineralocorticoids; D012333:RNA, Messenger; D000804:Angiotensin II; D003900:Desoxycorticosterone; D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase