Ghraf R, Schneider K, Kirchhoff J, Hiemke C
J Neurochem. 1982 Apr;38(4):876-83. doi: 10.1111/j.1471-4159.1982.tb05324.x.
Gonadectomy of male rats led to a threefold increase of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH) activity in pituitary homogenates that could be completely reversed by chronic administration of estradiol or 5 alpha-dihydrotestosterone (DHT). 3 alpha-HSDH was found to be distributed mainly between the 10,000 g and 100,000 g sediments from whole homogenates. The microsomal enzyme activity showed a substantial specificity for NADH whereas the cytosolic enzyme (100,000 g supernatant) demonstrated a slight preference for NADPH. The changes in Vmax found in homogenates following gonadectomy and gonadal steroid administration reflected changes in NADH-linked activity of the microsomal, but not the cytosolic enzyme. Estradiol-induced suppression of NADH-linked 3 alpha-HSDH activity in pituitary homogenates from gonadectomized rats of either sex was accompanied by a similar suppression of NADPH-linked 5 alpha-reductase activity and a marked decrease of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. In the ovariectomized rat chronic administration of nonsteroidal antiestrogens had strong estrogenic effects on 3 alpha-HSDH activity and LH release, but not on 5 alpha-reductase activity and FSH release. In the gonadectomized male rat, which was much less sensitive to intrinsic estrogenicity of the antiestrogens tested, nafoxidine completely blocked estradiol-induced suppression of 5 alpha-reductase activity and FSH release and partially antagonized suppression of LH release. The trans-isomeric, substituted triphenylethylenes, tamoxifen, and enclomiphene, as well as nitromifene (mixture of trans and cis isomers) were able partially to counteract estradiol-induced suppression of 5 alpha-reductase, but not 3 alpha-HSDH activity. It is concluded that estradiol action on pituitary 5 alpha-reductase, but not 3 alpha-HSDH activity, involves an estrogen receptor mechanism.
对雄性大鼠进行性腺切除后，垂体匀浆中3α-羟基类固醇脱氢酶（3α-HSDH）的活性增加了两倍，长期给予雌二醇或5α-二氢睾酮（DHT）可使其完全恢复。发现3α-HSDH主要分布在全匀浆10,000 g至100,000 g的沉淀物之间。微粒体酶活性对NADH具有较高的特异性，而胞质酶（100,000 g上清液）对NADPH表现出轻微的偏好。性腺切除和给予性腺类固醇后，匀浆中Vmax的变化反映了微粒体中与NADH相关的活性变化，而非胞质酶的变化。雌二醇诱导的去势大鼠垂体匀浆中与NADH相关的3α-HSDH活性抑制，伴随着与NADPH相关的5α-还原酶活性的类似抑制以及黄体生成素（LH）和促卵泡激素（FSH）释放的显著降低。在去卵巢大鼠中，长期给予非甾体类抗雌激素药物对3α-HSDH活性和LH释放具有强烈的雌激素作用，但对5α-还原酶活性和FSH释放无此作用。在对所测试的抗雌激素药物的内在雌激素活性不太敏感的去势雄性大鼠中，萘福昔定完全阻断了雌二醇诱导的5α-还原酶活性和FSH释放的抑制，并部分拮抗了LH释放的抑制。反式异构体、取代三苯乙烯、他莫昔芬和氯米芬，以及硝米芬（反式和顺式异构体的混合物）能够部分抵消雌二醇诱导的5α-还原酶抑制，但不能抵消3α-HSDH活性。结论是，雌二醇对垂体5α-还原酶活性的作用，而非对3α-HSDH活性的作用，涉及雌激素受体机制。
