Southren A L, Altman K, Vittek J, Boniuk V, Gordon G G
Invest Ophthalmol. 1976 Mar;15(3):222-8.
The metabolism of cortisol and other steroids was studied in normal untreated rabbit iris-ciliary body and cornea as part of an investigation into the mechanism of glucocorticoid-induced glaucoma. Cortisol is readily converted to the inactive metabolite cortisone by these eye tissues indicating the presence of an 11beta-oxidoreductase system. This reaction is reversible with cortisone being converted to cortisol in the presence of appropriate cofactor. However, due to the absence of a (or as yet undetectable) cortisol-A-ring-reductase system (rate-limiting reaction) the steroid is not irreversibly metabolized to biologically inactive compounds. The 11beta-oxidoreductase system readily converts other C21-11beta-hydroxysteroids, such as corticosterone, to its appropriate C21-11-ketosteroid (11-dehydrocorticosterone). Some C21-steroids lacking the 11-hydroxyl group (11-deoxycortisol, 11-deoxycorticosterone) remain virtually unmetabolized (exception to this was found with progesterone). Evidence of a C21-steroid A-ring reductase system was found only when cortisone and progesterone were used as substrates. However, testosterone a C19 steroid was converted to clearly identifiable A-ring reduced and 17beta-and 3alpha(beta)-oxidoreduced metabolites, thus indicating the presence of testosterone A-ring reductase, 17beta-and 3alpha(beta)-oxidoreductase systems in the eye tissues studied. The presence of a steroid 5alpha(beta)-reductase for some steroids but not for cortisol indicates a distinct substrate specificity for this enzyme system in the eye tissues.
作为对糖皮质激素性青光眼发病机制研究的一部分,我们对正常未处理的兔虹膜睫状体和角膜中皮质醇及其他类固醇的代谢进行了研究。这些眼组织能轻易地将皮质醇转化为无活性的代谢产物可的松,这表明存在11β-氧化还原酶系统。在适当辅因子存在的情况下,可的松可转化为皮质醇,此反应是可逆的。然而,由于缺乏(或尚未检测到)皮质醇A环还原酶系统(限速反应),该类固醇不会不可逆地代谢为生物无活性化合物。11β-氧化还原酶系统能轻易地将其他C21-11β-羟基类固醇,如皮质酮,转化为相应的C21-11-酮类固醇(11-脱氢皮质酮)。一些缺乏11-羟基的C21-类固醇(11-脱氧皮质醇、11-脱氧皮质酮)几乎未被代谢(孕酮是个例外)。仅当以可的松和孕酮为底物时,才发现有C21-类固醇A环还原酶系统的证据。然而,C19类固醇睾酮被转化为可明确识别的A环还原及17β-和3α(β)-氧化还原代谢产物,这表明在所研究的眼组织中存在睾酮A环还原酶、17β-和3α(β)-氧化还原酶系统。某些类固醇存在类固醇5α(β)-还原酶而皮质醇不存在,这表明该酶系统在眼组织中具有独特的底物特异性。