Bellido C, Aguilar R, Garrido-Gracia J C, Sánchez-Criado J E
Department of Cell Biology, Physiology and Immunology, University of Córdoba, Spain.
J Endocrinol Invest. 2002 Sep;25(8):702-8. doi: 10.1007/BF03345104.
The aim of the present study was to investigate the role of the estrogen (ES) background on the effects of P or its antagonist RU486 on basal and LHRH-stimulated LH and FSH secretion. To do this, pituitaries collected from: intact rats in proestrus; rats injected with the ES antagonist LY11701 8-HCl; rats injected with recombinant-human FSH (r-hFSH) to stimulate ovarian hormonogenesis; and rats injected with both LY11701 8-HCl and r-hFSH were incubated with or without LHRH (10 nM) in the presence of P (100 nM) or RU486 (10 nM). RU486 decreased basal and LHRH-stimulated release of LH and FSH and LHRH self-priming in pituitaries from control rats, while P increased both pituitary responsiveness and LHRH self-priming. These effects were absent in pituitaries from rats treated either with the ES antagonist or r-hFSH, which, in the absence of P or RU486 in the incubation medium, reduced gonadotropin release. Because r-hFSH did not increase E2 serum concentration significantly, the putative FSH-dependent ovarian non-steroidal gonadotropin surge inhibiting factor (GnSIF) might be the hormonal cause of the reduced secretion of LH and FSH. Combined treatment with LY117018-HCl and r-hFSH had additive inhibitory effects on gonadotropin release. These results indicate that ES-inducible P receptor (PR) in the pituitary can be activated in a ligand-independent manner by intracellular messengers giving rise to enhanced basal and LHRH-stimulated gonadotropin secretion. The results also suggested that the r-hFSH-stimulated ovarian bioactive entity GnSIF and RU486 may share a similar mechanism of action involving pituitary PR.
本研究的目的是探讨雌激素（ES）背景对孕激素（P）或其拮抗剂RU486对基础及促性腺激素释放激素（LHRH）刺激的促黄体生成素（LH）和促卵泡生成素（FSH）分泌的影响。为此，将从以下大鼠收集的垂体进行孵育：处于动情前期的完整大鼠；注射了ES拮抗剂LY11701 8 - HCl的大鼠；注射重组人促卵泡生成素（r - hFSH）以刺激卵巢激素生成的大鼠；以及同时注射了LY11701 8 - HCl和r - hFSH的大鼠，在有或无LHRH（10 nM）的情况下，于存在P（100 nM）或RU486（10 nM）的条件下进行孵育。RU486降低了对照大鼠垂体中基础及LHRH刺激的LH和FSH释放以及LHRH的自身启动作用，而P则增加了垂体反应性和LHRH的自身启动作用。在用ES拮抗剂或r - hFSH处理的大鼠的垂体中，这些作用不存在，在孵育培养基中不存在P或RU486的情况下，它们会降低促性腺激素释放。由于r - hFSH未显著增加血清雌二醇（E2）浓度，推测的FSH依赖性卵巢非甾体促性腺激素激增抑制因子（GnSIF）可能是LH和FSH分泌减少的激素原因。LY117018 - HCl和r - hFSH联合处理对促性腺激素释放具有累加抑制作用。这些结果表明，垂体中ES诱导的孕激素受体（PR）可被细胞内信使以不依赖配体的方式激活，从而导致基础及LHRH刺激的促性腺激素分泌增强。结果还提示，r - hFSH刺激的卵巢生物活性实体GnSIF和RU486可能具有涉及垂体PR的相似作用机制。
