Pieper D R, Gala R R, Schiff M A, Regiani S R, Marshall J C
Endocrinology. 1984 Sep;115(3):1190-6. doi: 10.1210/endo-115-3-1190.
Increased hypothalamic GnRH secretion appears to influence positively the number of pituitary GnRH receptors (GnRH-R). GnRH-R increase after castration in male rats, and this rise can be prevented by testosterone (T), anti-GnRH sera, or hypothalamic lesions. GnRH also increases serum LH and GnRH-R in hypothalamus-lesioned rats, and these animals injected with exogenous GnRH are, therefore, a good model in which to study the site of steroid feedback at the pituitary level. Adult male and female rats were gonadectomized, and radiofrequency lesions were placed in the hypothalamus. Males received T implants, and females received estradiol implants at the time of surgery. Empty capsules were placed in the control animals. Beginning 3-5 days later, animals in each group were injected every 8 h with vehicle (BSA) or GnRH (0.002-200 micrograms/day) for 2 days. After these GnRH injections, all rats received 6.6 micrograms GnRH, sc, 1 h before decapitation to determine acute LH and FSH responses. GnRH-R were determined by saturation analysis using 125I-D-Ala6-GnRH ethylamide as ligand. In males, GnRH injections increased GnRH-R. T inhibited acute LH and FSH responses to GnRH in all groups, but had little effect on GnRH-R, indicating that T inhibits gonadotropin secretion at a post-GnRH receptor site. In females, the GnRH-R response to GnRH was less marked, and only the 200 micrograms/day dose of GnRH increased GnRH-R, indicating that the positive feedback effects of estradiol at the pituitary level are also exerted at a site distal to the GnRH receptor. There was no positive correlation between the number of GnRH-R and GnRH-stimulated gonadotropin release in males or females. Female rats with hypothalamic lesions had markedly elevated serum PRL levels (greater than 300 ng/ml). Suppression of PRL secretion by bromocryptine resulted in augmented GnRH-R responses to GnRH, and GnRH-R concentrations rose to the same values induced in males. This suggests that hyperprolactinemia inhibits GnRH-R responses to GnRH in females by a direct action on the pituitary gonadotroph.
下丘脑促性腺激素释放激素（GnRH）分泌增加似乎对垂体GnRH受体（GnRH-R）的数量有正向影响。雄性大鼠去势后GnRH-R增加，而睾酮（T）、抗GnRH血清或下丘脑损伤可阻止这种增加。GnRH还可增加下丘脑损伤大鼠的血清促黄体生成素（LH）和GnRH-R，因此，给这些动物注射外源性GnRH是研究垂体水平类固醇反馈位点的良好模型。对成年雄性和雌性大鼠进行性腺切除，并在下丘脑放置射频损伤。雄性大鼠在手术时植入T，雌性大鼠植入雌二醇。给对照动物植入空胶囊。在3 - 5天后开始，每组动物每8小时注射一次溶剂（牛血清白蛋白）或GnRH（0.002 - 200微克/天），持续注射2天。在这些GnRH注射后，所有大鼠在断头前1小时皮下注射6.6微克GnRH，以测定急性LH和促卵泡生成素（FSH）反应。使用125I-D-丙氨酸6-GnRH乙酰胺作为配体，通过饱和分析测定GnRH-R。在雄性大鼠中，注射GnRH可增加GnRH-R。T抑制所有组对GnRH的急性LH和FSH反应，但对GnRH-R影响很小，表明T在GnRH受体后位点抑制促性腺激素分泌。在雌性大鼠中，对GnRH的GnRH-R反应不明显，只有200微克/天剂量的GnRH可增加GnRH-R，表明雌二醇在垂体水平的正反馈作用也在GnRH受体远端的位点发挥作用。在雄性或雌性大鼠中，GnRH-R的数量与GnRH刺激的促性腺激素释放之间没有正相关。下丘脑损伤的雌性大鼠血清催乳素（PRL）水平显著升高（大于300纳克/毫升）。用溴隐亭抑制PRL分泌导致对GnRH的GnRH-R反应增强，且GnRH-R浓度升至与雄性大鼠诱导的相同值。这表明高催乳素血症通过对垂体促性腺细胞的直接作用抑制雌性大鼠对GnRH的GnRH-R反应。
