INCREASED RATIO OF 5α-REDUCTASE: 3α(β)-HYDROXYSTEROID DEHYDROGENASE ACTIVITIES IN THE HYPERPLASTIC HUMAN PROSTATE

INCREASED RATIO OF 5α-REDUCTASE: 3α(β)-HYDROXYSTEROID DEHYDROGENASE ACTIVITIES IN THE HYPERPLASTIC HUMAN PROSTATE
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增生性人类前列腺中 5α-还原酶:3α(β)-羟基类固醇脱氢酶活性比例增加

DOI:
10.1677/joe.0.0800289
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发表时间:
1979
影响因子:
4
通讯作者:
G. Lieskovsky
G. Lieskovsky
中科院分区:
医学2区
文献类型:
--
作者:
N. Bruchovsky;G. Lieskovsky

文献摘要

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本文测定了8例正常前列腺、21例增生前列腺和4例癌前列腺组织匀浆中5 α-还原酶和3 α(β)-羟类固醇脱氢酶的活性。将含有300- 500 μ g组织蛋白的Tris缓冲液(pH 7.0)样品,在50 nM-[3 H]雄激素和NADPH生成系统(以5 × 10(-4)M-NADP开始)存在下,于37 ℃孵育30分钟。通过使用t.l.c.确定的5 α-和3 α-还原代谢物的产率和G.L.C.,给出了酶活性的估计值。在正常、增生和癌组织中表示5 α-还原酶活性的代谢物的形成分别为28.8 +/- 47(S.E.M.),76.8+/- 8.9和3.5 +/- 0.7 pmol 30 min-1 mg蛋白-1;类似地,表示3 α(β)-羟基类固醇脱氢酶活性的值为69.3 +/- 6.7、46.6 +/- 5.7和38.8 +/- 22.1 pmol 30 min-1 mg蛋白-1。在所有正常前列腺5 α-还原酶活性低于3 α(β)-羟基类固醇脱氢酶活性。相反,在21例增生性前列腺中的18例中,5 α-还原酶活性高于3 α(β)-羟基类固醇脱氢酶活性。5 α-还原酶活性增加而3 α(β)-羟基类固醇脱氢酶活性无代偿性变化的作用是改变5 α-还原酶和3 α(β)-羟基类固醇脱氢酶活性之间的平均比值,从正常前列腺中的0.47 +/- 0.11变为增生组织中的1.84 +/-0.19。据推测,这种变化可能使增生的前列腺雄激素代谢率不对称,从而导致双氢睾酮的异常积累。
: The activities of 5 alpha-reductase and 3 alpha (beta)-hydroxysteroid dehydrogenase were assayed in homogenates of eight normal, 21 hyperplastic and four carcinomatous human prostates. Samples consisting of 300--500 microgram tissue protein in Tris buffer, pH 7.0, were incubated at 37 degrees C for 30 min in the presence of 50 nM-[3H]androgen and an NADPH-generating system started with 5 X 10(-4)M-NADP. The yield of 5 alpha- and 3 alpha-reduced metabolites, as established by using t.l.c. and g.l.c., gave an estimate of enzyme activity. The formation of metabolites denoting 5 alpha-reductase activity in normal, hyperplastic and carcinomatous tissue respectively was 28.8 +/- 47 (S.E.M.), 76.8 +/- 8.9 and 3.5 +/- 0.7 pmol 30 min-1 mg protein-1; similarly, that denoting 3 alpha (beta)-hydroxysteroid dehydrogenase activity was 69.3 +/- 6.7, 46.6 +/- 5.7 and 38.8 +/- 22.1 pmol 30 min-1 mg protein-1. In all normal prostates 5 alpha-reductase activity was lower than 3 alpha (beta)-hydroxysteroid dehydrogenase activity. Conversely, in 18 out of 21 hyperplastic prostates, 5 alpha-reductase activity was higher than 3 alpha (beta)-hydroxysteroid dehydrogenase activity. The effect of the increase in 5 alpha-reductase activity without a compensatory change in 3 alpha (beta)-hydroxysteroid dehydrogenase activity was to alter the mean ratio between 5 alpha-reductase and 3 alpha (beta)-hydroxysteriod dehydrogenase activities from 0.47 +/- 0.11 in the normal prostate to 1.84 +/- 0,19 in hyperplastic tissue. It is inferred that this change may predispose the hyperplastic prostate to asymmetrical rates of androgen metabolism and thereby contribute to the abnormal accumulation of dihydrotestosterone.