Hypothalamus-pituitary-ovarian axis in cyclic rats lacking progesterone actions.
Hypothalamus-pituitary-ovarian axis in cyclic rats lacking progesterone actions.
复制标题
缺乏黄体酮作用的周期性大鼠的下丘脑-垂体-卵巢轴。
作者：
J. Sánchez;F. Galiot;C. Bellido;D. González;M. Tébar
s.c.对周期性大鼠动情间期孕酮的拮抗作用。注射抗孕酮RU 486（从动情后期到动情前期每天两次，每次2 mg）增加LH和降低FSH基础血清浓度。动情后期（0800小时）卵巢切除术增加血清中的两种促性腺激素在控制和逆转RU 486诱导的基础促性腺激素分泌的解离。RU 486-解离的促性腺激素分泌也依赖于LHRH，因为处理（s.c.）在动情后期和动情间期每天两次用1 mg GnRH拮抗剂（ORG 30276）完全阻止了RU 486引起的LH升高和FSH血清浓度降低。在动情前期早晨，RU 486处理的大鼠下丘脑内侧基底部和正中隆起的LHRH含量增加。LH垂体对25 ng LHRH（半岛7201;半岛实验室，Merseyside，UK）在用RU 486处理的大鼠中在间情期1700 h时增强。在油注射大鼠中，垂体FSH反应无差异。在发情前期早晨，RU 486处理的大鼠垂体中两种促性腺激素的含量均降低。所有这些影响，由于RU 486在周期性大鼠被逆转卵巢切除术。从间情期开始，血清睾酮水平显著升高，在RU 486处理的大鼠中，雌二醇浓度在发情前期早晨升高。卵巢切除术以及LHRH拮抗剂治疗消除了RU 486对卵巢类固醇产生的影响。此外，抗雌激素他莫昔芬治疗逆转了RU 486解离的促性腺激素分泌，而抗雄激素氟西汀治疗没有影响。该实验的结果证实了先前的发现，即RU 486处理使周期性大鼠的基础促性腺激素分泌解离。此外，本研究结果还表明：（1）RU 486的这种作用不是由于该化合物的直接作用，也不是由于在中枢水平阻断孕酮的作用;（2）RU 486对垂体促性腺激素分泌的作用依赖于卵巢物质，而不是孕酮和LHRH，因为它被卵巢切除术逆转，并被LHRH拮抗剂治疗完全消除;（3）RU 486降低大鼠血清FSH水平的作用可能是由垂体水平的雌二醇和雌二醇通过减少FSH的合成和分泌而实现的;和（4）与卵巢切除术引起的LH分泌相比，用RU 486处理的大鼠中LH分泌过多似乎是以下原因的结果：首先，孕酮对LH分泌缺乏抑制作用，第二，不适当的反馈系统，包括在异常高水平的睾酮存在下，下丘脑LHRH活性和垂体对中等高水平雌二醇的LHRH敏感性增加。
Antagonizing diestrous progesterone actions in cyclic rats by s.c. injections of the antiprogesterone RU486 (2 mg twice a day from metestrus through proestrus) increased LH and decreased FSH basal serum concentrations. Ovariectomy at metestrus (0800 h) increased serum levels of both gonadotropins in controls and reversed the RU486-induced dissociation of basal gonadotropin secretion. RU486-dissociated gonadotropin secretion is also dependent upon LHRH, since treatment (s.c.) with 1 mg GnRH antagonist (ORG 30276) twice a day on metestrus and diestrus completely prevented both the RU486-induced increase in LH and the decrease in FSH serum concentrations. The LHRH content in the medial basal hypothalamus and median eminence increased on proestrous morning in RU486-treated rats. The LH pituitary response to an exogenous i.v. bolus of 25 ng LHRH (Peninsula 7201; Peninsula Laboratory, Inc., Merseyside, UK) at 1700 h on diestrus was enhanced in rats treated with RU486. No differences in pituitary FSH response were noted with respect to oil-injected rats. The pituitary content of both gonadotropins decreased in RU486-treated rats on proestrous morning. All these effects due to RU486 in cyclic rats were reversed by ovariectomy. Testosterone serum levels increased significantly from diestrus onward, and the estradiol concentration increased on proestrous morning in RU486-treated rats. Ovariectomy as well as LHRH antagonist treatment eliminated the effects of RU486 on ovarian steroid production. Moreover, antiestrogen tamoxifen treatment reversed RU486-dissociated gonadotropin secretion, while antiandrogen flutamide treatment had no effect. The results of this experiment have confirmed previous findings that RU486 treatment dissociates basal gonadotropin secretion in cyclic rats. In addition, the present results show that: (1) this effect of RU486 is not due to a direct effect of this compound or to the blockade of progesterone action at a central level; (2) the effect of RU486 on pituitary gonadotropin secretion depends on ovarian substances other than progesterone and LHRH, since it is reversed by ovariectomy and completely abolished by LHRH antagonist treatment; (3) the reduction in FSH serum levels in rats treated with RU486 seems to be exerted by inhibin and estradiol at the pituitary level by reducing FSH synthesis and secretion; and (4) the hypersecretion of LH in rats treated with RU486, as compared to that resulting from ovariectomy, seems to be the consequence of, first, a lack of progesterone inhibitory action on LH secretion, and, second, an inappropriate feedback system involving increased hypothalamic LHRH activity and pituitary sensitivity to LHRH of moderately high levels of estradiol in the presence of abnormally high levels of testosterone.
给大鼠施用抗黄体生成素释放激素血清：对黄体生成素和卵泡刺激素围排卵分泌的影响。
影响因子：
4.8
作者：
Blake,CA;Kelch,RP
通讯作者：
Kelch,RP