Premium
Subcellular Distribution of 3α‐Hydroxysteroid Dehydrogenase and Antiestrogen Action on Androgen‐Metabolizing Enzymes in Rat Pituitary Gland
Author(s) -
Ghraf Rüdiger,
Schneider Klaus,
Kirchhoff Josef,
Hiemke Christoph
Publication year - 1982
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1982.tb05324.x
Subject(s) - medicine , endocrinology , luteinizing hormone , cytosol , microsome , antiestrogen , chemistry , follicle stimulating hormone , dihydrotestosterone , enzyme , ovariectomized rat , estrogen , hormone , androgen , biology , tamoxifen , biochemistry , cancer , breast cancer
Gonadectomy of male rats led to a threefold increase of 3α‐hydroxysteroid dehydrogenase (3α‐HSDH) activity in pituitary homogenates that could be completely reversed by chronic administration of estradiol or 5α‐dihydrotestosterone (DHT). 3α‐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 V max 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 3α‐HSDH activity in pituitary homogenates from gonadectomized rats of either sex was accompanied by a similar suppression of NADPH‐linked 5α‐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 3α‐HSDH activity and LH release, but not on 5α‐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 5α‐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 5α‐reductase, but not 3α‐HSDH activity. It is concluded that estradiol action on pituitary 5α‐reductase, but not 3α‐HSDH activity, involves an estrogen receptor mechanism.