Noguchi K
Department of Urology, Yokohama City University, School of Medicine, Japan.
Nihon Naibunpi Gakkai Zasshi. 1987 Nov 20;63(11):1341-50. doi: 10.1507/endocrine1927.63.11_1341.
To determine whether dihydrotestosterone (DHT) or estradiol (E2) exerts negative or positive feedback effects on rat pituitary gland, Testosterone (T) metabolite (T, DHT, 5 alpha-androstane-3 alpha, 17 beta-diol:3 alpha-diol or E2) was added to the cultured pituitary cells. Anterior pituitary glands were obtained from 6-week-old male rats. Pituitary cells were prepared by trypsin digestion and incubated with various concentrations of steroid hormones for 72 h to determine the effects of steroid hormones on basal secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) after 48 h preculture without steroids. Then 10 nM luteinizing hormone-releasing hormone (LH-RH) with appropriate concentrations of these steroid hormones was added to the pituitary cells in culture and incubated for another 6h to determine the effects of steroid hormones on LH-RH induced gonadotropin release. After the incubation, pituitary cells were lysed with 0.1% Triton X100 to measure the intracellular gonadotropin content. The concentration of LH and FSH was determined by radioimmunoassay. T, DHT and 3 alpha-diol stimulated basal FSH but not basal LH secretion, and inhibited both the release of FSH and LH from cultured pituitary cells during incubations with LH-RH in a dose-dependent fashion. Intracellular content of both FSH and LH were increased, and total FSH and not LH was also increased by the addition of DHT in a dose-dependent manner. E2 did not exert any of such effects on pituitary cells in culture. These studies suggest that 5 alpha-reduced metabolites but not aromatized metabolite of T play an important role on feedback regulation of gonadotropin secretion at pituitary level. DHT directly acts on pituitary gland not only to stimulate the production of FSH but also to suppress FSH and LH secretion induced by LH-RH.
为了确定双氢睾酮(DHT)或雌二醇(E2)对大鼠垂体是产生负反馈还是正反馈作用,将睾酮(T)代谢物(T、DHT、5α-雄甾烷-3α,17β-二醇:3α-二醇或E2)添加到培养的垂体细胞中。从6周龄雄性大鼠获取垂体前叶。通过胰蛋白酶消化制备垂体细胞,并在无类固醇预培养48小时后,与不同浓度的类固醇激素孵育72小时,以确定类固醇激素对黄体生成素(LH)和促卵泡激素(FSH)基础分泌的影响。然后将10 nM促黄体生成素释放激素(LH-RH)与这些类固醇激素的适当浓度添加到培养的垂体细胞中,再孵育6小时,以确定类固醇激素对LH-RH诱导的促性腺激素释放的影响。孵育后,用0.1% Triton X100裂解垂体细胞以测量细胞内促性腺激素含量。通过放射免疫测定法测定LH和FSH的浓度。T、DHT和3α-二醇刺激基础FSH分泌,但不刺激基础LH分泌,并在与LH-RH孵育期间以剂量依赖性方式抑制培养的垂体细胞中FSH和LH的释放。添加DHT以剂量依赖性方式增加FSH和LH的细胞内含量,并且总FSH增加而LH不增加。E2对培养的垂体细胞未产生任何此类作用。这些研究表明,T的5α-还原代谢物而非芳香化代谢物在垂体水平对促性腺激素分泌的反馈调节中起重要作用。DHT直接作用于垂体,不仅刺激FSH的产生,还抑制LH-RH诱导的FSH和LH分泌。