Es-souni Routhier M, Bournot P, Ramirez L C
Laboratoire de Biochimie, Faculté des Sciences, Université de Bourgogne, Dijon, France.
J Steroid Biochem Mol Biol. 1995 Jun;52(6):581-5. doi: 10.1016/0960-0760(95)00009-o.
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.
Y-1肾上腺细胞系可从脱氧皮质酮生成20α-二氢醛固酮。通过与先前合成的参考化合物进行比较，利用气相色谱-质谱联用仪（GC-MS）鉴定了该化合物。另外两种18-羟基化代谢产物分别被鉴定为源自内源性胆固醇的11β,18-二羟基-20α-二氢孕酮以及源自脱氧皮质酮（DOC）的18-羟基-20α-二氢-11-脱氢皮质酮。合成这些化合物所需的条件是在补充有20%血清的培养基中培养，并与底物反复孵育。促肾上腺皮质激素（ACTH）和血管紧张素II对11β-羟基化类固醇和18-氧化类固醇生成的刺激作用不同，这表明存在两种不同的酶，即细胞色素P-450(11)β和细胞色素P-450aldo的表达。Y-1细胞系既可以分泌糖皮质激素途径特有的11β-羟基化类固醇，也可以分泌盐皮质激素途径特有的18-氧化类固醇，而在体内这些类固醇通常是在肾上腺皮质的两个不同区域产生的。该细胞系应该是研究调节参与类固醇生成途径最后步骤的这两种酶表达的分子机制的一个有趣模型。
