Koppenaal D W, van Dieten J A, Tijssen A M, de Koning J
Division of Medical Pharmacology of the Leiden/Amsterdam Center for Drug Research, University of Leiden, Sylvius Laboratory, The Netherlands.
J Endocrinol. 1993 Aug;138(2):191-201. doi: 10.1677/joe.0.1380191.
This study was designed to explore the efficacy of gonadotrophin-releasing hormone (GnRH) to antagonize the effect of gonadotrophin surge-inhibiting factor (GnSIF) on the timing of the induction by GnRH of the maximal self-priming effect on pituitary LH responsiveness. The GnSIF levels were increased by FSH treatment and reduced after gonadectomy. Female rats were injected s.c. with 10 IU FSH or saline (control) on three occasions during the 4-day cycle. Serial i.v. injections of GnRH (500 pmol/kg body weight) were administered to intact rats on the afternoon of pro-oestrus or 15-30 min after ovariectomy. Intact male rats were given 10 IU FSH and 500 or 2000 pmol GnRH/kg body weight on an equivalent time-schedule. Endogenous GnRH release was suppressed with phenobarbital. In intact female control rats, the timing of the maximally primed LH response was delayed as the GnRH pulse-interval increased. FSH treatment of female rats induced a suppression of the initial unprimed LH response and delayed the maximally primed LH response, which showed further delay as the GnRH pulse-interval was increased. When the pulsatile administration of GnRH was started 15-30 min after ovariectomy, the priming effect of GnRH did not change as the GnRH pulse-interval was increased in the saline-treated rats. However, FSH treatment caused a suppression of the unprimed LH response, a delay in the primed LH response and decreased the delay of the maximally primed LH response to GnRH when the GnRH pulse-interval was decreased. Increasing the interval between ovariectomy and the first GnRH pulse to 4 h diminished the efficacy of the FSH treatment: GnRH-induced priming was delayed by only one pulse instead of the two pulses in control rats. In intact males but not in orchidectomized rats, a self-priming effect was demonstrated during GnRH pulses which were 1 h apart. The effect of 2 nmol GnRH/kg body weight was the most pronounced. Compared with intact female rats, the timing of the maximally primed LH response was delayed by 1 h. FSH treatment did not affect the pituitary LH response to both dose levels of GnRH. It is concluded that FSH treatment increased the release of GnSIF by the ovary, then induced a state of low responsiveness of the pituitary gland to GnRH and subsequently delayed GnRH-induced maximal self-priming. The efficacy of GnRH to prime the pituitary gland was higher when GnSIF levels were decreasing after removal of the ovaries.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究旨在探讨促性腺激素释放激素(GnRH)拮抗促性腺激素激增抑制因子(GnSIF)对GnRH诱导垂体促黄体生成素(LH)反应最大自身预激发效应时间的影响。通过促卵泡生成素(FSH)处理可使GnSIF水平升高,而性腺切除术后GnSIF水平降低。在4天的周期中,对雌性大鼠皮下注射3次10 IU FSH或生理盐水(对照)。在动情前期下午或卵巢切除术后15 - 30分钟,对完整大鼠进行静脉连续注射GnRH(500 pmol/kg体重)。对完整雄性大鼠按相同时间安排给予10 IU FSH和500或2000 pmol GnRH/kg体重。用苯巴比妥抑制内源性GnRH释放。在完整雌性对照大鼠中,随着GnRH脉冲间隔增加,最大预激发LH反应的时间延迟。对雌性大鼠进行FSH处理可抑制初始未预激发的LH反应,并延迟最大预激发LH反应,随着GnRH脉冲间隔增加,这种延迟进一步加大。当在卵巢切除术后15 - 30分钟开始脉冲式注射GnRH时,在生理盐水处理的大鼠中,随着GnRH脉冲间隔增加,GnRH的预激发效应不变。然而,FSH处理会抑制未预激发的LH反应,延迟预激发的LH反应,并且当GnRH脉冲间隔减小时,会减少最大预激发LH反应对GnRH的延迟。将卵巢切除与首次GnRH脉冲之间的间隔延长至4小时会降低FSH处理的效果:GnRH诱导的预激发仅延迟一个脉冲,而不是对照大鼠中的两个脉冲。在完整雄性大鼠而非去势大鼠中,在间隔1小时的GnRH脉冲期间可显示自身预激发效应。2 nmol GnRH/kg体重的效果最为明显。与完整雌性大鼠相比,最大预激发LH反应的时间延迟1小时。FSH处理不影响垂体对两种剂量水平GnRH的LH反应。结论是,FSH处理增加了卵巢GnSIF的释放,进而诱导垂体对GnRH的低反应状态,随后延迟GnRH诱导的最大自身预激发。当卵巢切除后GnSIF水平下降时,GnRH对垂体的预激发效果更高。(摘要截短至400字)