HUMAN HEPATIC CORTISOL REDUCTASE ACTIVITIES - ENZYMATIC-PROPERTIES AND SUBSTRATE SPECIFICITIES OF CYTOSOLIC CORTISOL DELTA-4-5-BETA-REDUCTASE AND DIHYDROCORTISOL-3-ALPHA-OXIDOREDUCTASE(S)

被引：22

作者：

IYER, RB ^{[1
]}

BINSTOCK, JM ^{[1
]}

SCHWARTZ, IS ^{[1
]}

GORDON, GG ^{[1
]}

WEINSTEIN, BI ^{[1
]}

SOUTHREN, AL ^{[1
]}

机构：

[1] NEW YORK MED COLL,DEPT MED,VALHALLA,NY 10595

来源：

STEROIDS | 1990年 / 55卷 / 11期

关键词：

STEROIDS; REDUCTASES; HEPATIC REDUCTASES; CORTISOL;

D O I：

10.1016/0039-128X(90)90087-R

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The metabolism of cortisol by human liver homogenates has been studied. Cortisol DELTA-4-reductase and dihydrocortisol-3-oxidoreductase activities were distributed in all subcellular fractions. The products of the soluble enzymes were identified. Cortisol and 5-beta-dihydrocortisol were reduced to 3-alpha,5-beta-tetrahydrocortisol, and 5-alpha-dihydrocortisol was reduced to 3-alpha, 5-alpha-tetrahydrocortisol. The soluble enzymes showed a wide range of substrate specificity. The 21 substituted cortisol derivatives were not metabolized. The apparent Km values of cortisol DELTA-4-5-beta-reductase and dihydrocortisol-3-alpha-oxidoreductase for their substrates (cortisol, 5-alpha-dihydrocortisol, and 5-beta-dihydrocortisol) all ranged from 18 to 27-mu-M. Dexamethasone inhibited the reduction of all of these substrates and the inhibition was abolished by 21 substitution of the dexamethasone. Testosterone was a competitive inhibitor of the reduction of cortisol, 5-alpha-dihydrocortisol, and 5-beta-dihydrocortisol with a K(i) ranging from 11 to 32-mu-M. NADPH was the preferred cofactor for the cortisol DELTA-4-5-beta-reductase and dihydrocortisol-3-alpha-oxidoreductase. No end product inhibition was observed.

引用

页码：495 / 500

页数：6

共 36 条

[1] Marver, Edelman, Dihydrocortisol: a potential mineralocorticoid, J Steroid Biochem, 9, pp. 1-7, (1978)
[2] Adam, Funder, Mercer, Ulick, Amplification of the action of aldosterone by 5α-dihydrocortisol, Endocrinology, 103, pp. 465-471, (1978)
[3] Weinstein, Gordon, Southren, Potentiation of glucocorticoid activity by 5β-dihydrocortisol: its role in glaucoma, Science, 222, pp. 172-173, (1983)
[4] Southren, Gordon, l'Hommedieu, Ravikumar, Dunn, Weinstein, 5β-Dihydrocortisol: possible mediator of the ocular hypertension in glaucoma, Invest Ophthalmol Vis Sci, 26, pp. 393-395, (1985)
[5] Southren, Hernandez, l'Hommedieu, Gordon, Weinstein, Potentiation of collagen synthesis in explants of the rabbit eye by 5β-dihydrocortisol, Invest Ophthalmol Vis Sci, 27, pp. 1757-1760, (1986)
[6] Southren, l'Hommedieu, Gordon, Weinstein, Intraocular hypotensive effect of a topically applied cortisol metabolite: 3α, 5β-tetrahydrocortisol, Invest Ophthalmol Vis Sci, 28, pp. 901-903, (1987)
[7] Feder, Marrone, Progesterone: its role in the central nervous system as a facilitator and inhibitor of sexual and gonadotropin release, Ann NY Acad Sci, 286, pp. 331-354, (1977)
[8] Kubli-Garfias, Whalen, Induction of lordosis behavior in female rats by intravenous administration of progestins, Harm Behav, 9, pp. 380-386, (1977)
[9] Kubli-Garfias, Medrano-Conde, Beyer, Bondani, In vitro inhibition of rat uterine contractility induced by 5α- and 5β-progestins, Steroids, 34, pp. 609-617, (1979)
[10] Mainwaring, The mechanism of action of androgens, Monographs on Endocrinology, 10, pp. 25-29, (1977)

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