Lathe Richard
Division of Biomedical Sciences, University of Edinburgh, George Square, EH9 9XD, Edinburgh, UK.
Steroids. 2002 Nov;67(12):967-77. doi: 10.1016/s0039-128x(02)00044-2.
B-ring hydroxylation is a major metabolic pathway for cholesterols and some steroids. In liver, 7 alpha-hydroxylation of cholesterols, mediated by CYP7A and CYP39A1, is the rate-limiting step of bile acid synthesis and metabolic elimination. In brain and other tissues, both sterols and some steroids including dehydroepiandrosterone (DHEA) are prominently 7 alpha-hydroxylated by CYP7B. The function of extra-hepatic steroid and sterol 7-hydroxylation is unknown. Nevertheless, 7-oxygenated cholesterols are potent regulators of cell proliferation and apoptosis; 7-oxygenated derivatives of DHEA, pregnenolone, and androstenediol can have major effects in the brain and in the immune system. The receptor targets involved remain obscure. It is argued that B-ring modification predated steroid evolution: non-enzymatic oxidation of membrane sterols primarily results in 7-oxygenation. Such molecules may have provided early growth and stress signals; a relic may be found in hydroxylation at the symmetrical 11-position of glucocorticoids. Early receptor targets probably included intracellular sterol sites, some modern steroids may continue to act at these targets. 7-Hydroxylation of DHEA may reflect conservation of an early signaling pathway.
B环羟基化是胆固醇和一些甾体的主要代谢途径。在肝脏中，由CYP7A和CYP39A1介导的胆固醇7α-羟基化是胆汁酸合成和代谢消除的限速步骤。在脑和其他组织中，甾体和一些甾体（包括脱氢表雄酮，DHEA）均被CYP7B显著地7α-羟基化。肝外甾体和甾醇7-羟基化的功能尚不清楚。然而，7-氧化胆固醇是细胞增殖和凋亡的有效调节剂；DHEA、孕烯醇酮和雄烯二醇的7-氧化衍生物可在脑和免疫系统中产生重大影响。所涉及的受体靶点仍不清楚。有人认为B环修饰早于甾体的进化：膜甾醇的非酶氧化主要导致7-氧化。这类分子可能提供了早期生长和应激信号；在糖皮质激素对称的11位羟基化中可能发现了一种遗迹。早期的受体靶点可能包括细胞内甾醇位点，一些现代甾体可能继续作用于这些靶点。DHEA的7-羟基化可能反映了早期信号通路的保守性。
