School of Veterinary Science, University of Liverpool, Leahurst Campus, Neston, Wirral CH64 7TE, UK.
Physiol Behav. 2012 Feb 1;105(3):757-65. doi: 10.1016/j.physbeh.2011.09.025. Epub 2011 Oct 8.
Acute insulin administration causes a disparity between the onset of estrous behavior and the LH surge in ovary-intact ewes. To examine the considerable variation in responses, in the present study we used a large number of animals to confirm findings with insulin, and examine whether endotoxin has the same effect. During the breeding season, follicular phases of intact ewes were synchronized with progesterone vaginal pessaries and received saline vehicle (n=22; controls), insulin (4 IU/kg; n=21 ewes) or endotoxin (LPS; 100 ng/kg; n=10) at 28 h after progesterone withdrawal (time zero). In controls, the LH surge onset occurred at 36.5±5.7 h and were first mounted by a ram at 38.2±1.8 h, but there was a delay of 17.6 h (P<0.001) and 7.2 h (P<0.05), respectively, in half the insulin-treated animals ('insulin-delayed') but not in the other half; and a delay of 22.5 h (P<0.001) and 20.7h (P<0.001), respectively, in all LPS-treated animals. Plasma estradiol concentrations decreased after both stressors, and remained low for a period of time equivalent to the LH surge delay (P<0.001; Rs-q=78%). Cortisol increased for 12h after treatment in both insulin subgroups and the LPS group (P<0.05); whereas progesterone increased in the insulin-delayed and LPS groups from 4.0±0.5 ng/ml and 5.3±1.0 ng/ml to a maximum of 5.7±0.3 ng/ml and 8.8±1.6 ng/ml, respectively (P<0.05 for both comparisons). Plasma triglycerides were measured to assess insulin resistance, but concentrations were similar before and after treatment (0.25±0.01 mmol/l versus 0.21±0.01 and 0.25±0.01 mmol/l versus 0.26±0.01 mmol/l in the insulin-non delayed and insulin delayed subgroups, respectively). Therefore, we hypothesize that a) when an acute stressor is applied during the late follicular phase, the duration of the LH surge delay is related to the duration of estradiol signal disruption b) cortisol is not the key disruptor of the LH surge after insulin, c) insulin (but not LPS) can separate the onsets of LH surge and estrus by approximately 10h, providing a model to identify the specific neuronal systems that control behavior distinct from those initiating the GnRH surge.
急性胰岛素给药会导致卵巢完整的母羊发情行为的开始和 LH 峰之间出现差异。为了研究这种反应的巨大差异，本研究使用了大量动物来证实胰岛素的发现，并研究内毒素是否具有相同的作用。在繁殖季节，用孕酮阴道栓剂同步完整母羊的卵泡期，并在孕酮撤药后 28 小时（零时）给予生理盐水载体（n=22；对照组）、胰岛素（4IU/kg；n=21 只母羊）或内毒素（LPS；100ng/kg；n=10）。在对照组中，LH 峰的出现时间为 36.5±5.7 小时，母羊第一次被公羊骑跨的时间为 38.2±1.8 小时，但有一半接受胰岛素治疗的动物（“胰岛素延迟”）分别延迟了 17.6 小时（P<0.001）和 7.2 小时（P<0.05），而另一半则没有；并且所有 LPS 处理的动物分别延迟了 22.5 小时（P<0.001）和 20.7 小时（P<0.001）。两种应激源后血浆雌二醇浓度下降，并在相当于 LH 峰延迟的时间内保持低水平（P<0.001；Rs-q=78%）。胰岛素亚组和 LPS 组的皮质醇在治疗后 12 小时内升高（P<0.05）；而胰岛素延迟和 LPS 组的孕酮从 4.0±0.5ng/ml 和 5.3±1.0ng/ml 增加到最大 5.7±0.3ng/ml 和 8.8±1.6ng/ml（两种比较均 P<0.05）。测量血浆甘油三酯以评估胰岛素抵抗，但治疗前后浓度相似（胰岛素非延迟亚组为 0.25±0.01mmol/l，胰岛素延迟亚组为 0.21±0.01mmol/l 和 0.25±0.01mmol/l；分别）。因此，我们假设：a）当在卵泡晚期应用急性应激源时，LH 峰延迟的持续时间与雌二醇信号中断的持续时间有关；b）皮质醇不是胰岛素后 LH 峰中断的关键因素；c）胰岛素（但不是 LPS）可以将 LH 峰和发情的开始分离约 10 小时，提供了一个模型来识别控制与启动 GnRH 峰不同的行为的特定神经元系统。
