Phillips D J, Cummins J T, Clarke I J
Monash Medical Centre, Prince Henry's Hospital Campus, Melbourne, Victoria, Australia.
J Endocrinol. 1990 Nov;127(2):223-33. doi: 10.1677/joe.0.1270223.
The patterns of gonadotrophin-releasing hormone (GnRH) input to the pituitary gland that affect the expression of a positive-feedback event by oestrogen on LH secretion were investigated in ovariectomized ewes with hypothalamo-pituitary disconnection (HPD). In experiment 1, ovariectomized HPD ewes were given hourly i.v. pulses of 250 ng GnRH and an i.m. injection of 50 micrograms oestradiol benzoate (OB). The ewes were given a bolus pulse of 2.25 micrograms GnRH 16 h after injection of OB, followed by half-hourly pulses of 250 ng GnRH for 14 h (treatment A). The LH surge response was significantly (P less than 0.05) greater in these ewes compared with that in ewes given a continuous infusion of GnRH (250 ng/h) after the OB injection, followed by a continuous infusion of 500 ng GnRH/h after the bolus pulse of GnRH (treatment B). When no GnRH was administered after the OB injection, except for the bolus pulse of GnRH (treatment C), the surge response was significantly (P less than 0.05) reduced compared with that in treatment A, and was reduced compared with treatment B. These data suggest that GnRH pulses are important in the generation of the OB-induced LH surge, but that a baseline secretory component can prime the pituitary to some extent. In experiment 2, a doubling of the continuous infusion dose of GnRH used in treatment B to 500 ng/h before the bolus pulse of GnRH and to 1 micrograms/h afterwards (treatment D) gave a similar response compared with treatment A, suggesting that if the baseline input of GnRH is of sufficient magnitude, it can overcome the lack of pulsatile input. In experiment 3, halving the GnRH pulse amplitude used in treatment A from 250 to 125 ng (treatment E) did not reduce the LH surge response, implying that when the GnRH input is in a pulsatile mode, the amplitude of GnRH pulses is less important than the pulsatile nature per se. In experiment 4, removal of GnRH input after the bolus pulse of GnRH (treatment F) significantly (P less than 0.05) reduced the surge response compared with when pulses were maintained (treatment A), indicating that GnRH input is still required once the LH surge has been initiated. Collectively, these experiments show that several forms of GnRH delivery, both pulsatile and baseline, can result in the full expression of a positive-feedback response in ovariectomized ewes treated with oestrogen.
在患有下丘脑 - 垂体分离(HPD)的去卵巢母羊中,研究了促性腺激素释放激素(GnRH)输入垂体的模式,该模式影响雌激素对促黄体生成素(LH)分泌的正反馈事件的表达。在实验1中,给去卵巢的HPD母羊每小时静脉注射250 ng GnRH,并肌肉注射50微克苯甲酸雌二醇(OB)。在注射OB后16小时,给母羊静脉推注2.25微克GnRH,随后每半小时静脉注射250 ng GnRH,持续14小时(处理A)。与在注射OB后持续输注GnRH(250 ng/h),然后在GnRH推注脉冲后持续输注500 ng GnRH/h的母羊(处理B)相比,这些母羊的LH峰反应显著更高(P<0.05)。当在注射OB后,除了GnRH推注脉冲外不给予GnRH时(处理C),峰反应与处理A相比显著降低(P<0.05),并且与处理B相比也降低。这些数据表明,GnRH脉冲在OB诱导的LH峰的产生中很重要,但基线分泌成分可以在一定程度上使垂体致敏。在实验2中,在GnRH推注脉冲前将处理B中使用的GnRH持续输注剂量加倍至500 ng/h,之后加倍至1微克/h(处理D),与处理A相比产生了相似的反应,这表明如果GnRH的基线输入量足够大,它可以克服缺乏脉冲式输入的影响。在实验3中,将处理A中使用的GnRH脉冲幅度从250 ng减半至125 ng(处理E)并没有降低LH峰反应,这意味着当GnRH输入处于脉冲模式时,GnRH脉冲的幅度比脉冲本身的性质更不重要。在实验4中,与维持脉冲时(处理A)相比,在GnRH推注脉冲后去除GnRH输入(处理F)显著降低了峰反应(P<0.05),表明一旦启动LH峰,仍然需要GnRH输入。总体而言,这些实验表明,几种形式的GnRH递送,包括脉冲式和基线式,都可以在接受雌激素处理卵巢切除的母羊中导致正反馈反应的充分表达。