Brain mechanism responsible for the suppression of reproduction by malnutrition and fasting

本研究旨在探讨营养不良和禁食抑制生殖的机制。我们之前已经表明，禁食以雌激素依赖的方式抑制大鼠促黄体生成素(LH)的脉动性释放。我们还报道了下丘脑室旁核(PVN)是参与禁食抑制黄体生成素(LH)的雌激素作用部位，禁食和糖化可诱导PVN中雌激素受体a(Era)的表达。本研究表明，禁食和糖化诱导的ERA在PVN的表达是由投射到PVN的去甲肾上腺素能神经元介导的。此外，本研究还表明，去甲肾上腺素能神经元投射到终纹床核(BNST)可能参与了营养不良时黄体生成素分泌的抑制。结果表明，禁食可抑制山羊的多单位活动(MUA)。在山羊体内，黑素皮质素系统可能参与生殖的能量调节。最后，本研究发现，作为GPR54天然配体的一种新的神经肽，Matastin在生殖调节中起着中心作用，因为Metastin介导了大鼠排卵前的促黄体生成素释放。最近的研究结果表明，抑制哺乳期大鼠促黄体生成素的搏动性释放主要是由于抑制了脑组织中Metastin的表达。

The present study was performed to investigate the mechanism mediating suppression of reproduction by malnutrition and fasting. We have previously shown that fasting suppresses pulsatile release of luteinizing hormone (LH) in an estrogen-dependent manner in the rat. We also reported that the paraventricular nucleus of the hypothalamus (PVN) is an estrogen action site involved in the fasting-induced suppression of LH and that fasting and glucoprivation induces estrogen receptor a (ERa) expression in the PVN. The present study revealed that fasting- and glucopiviation-induced expression of ERa in the PVN was mediated by noradrenergic neurons projecting to the PVN. Furthermore, the present study showed the posibility that noradrenergic neurons projecting to the bed nucleus of the stria terminalis (BNST) may mediate the suppression of LH secretion during malnutrition.It was shown that the multiple unit activity (MUA), as an indicator of the activity of reproduction, was suppressed by fasting in the goat. We also showed the posibility in the goat that melanocortin system may be involved in the energetic regulation of reproduction.Finally, the present study revealed that matastin, a novel neuropeptice which is a natural ligand for GPR54, plays a central role in regulation of reproduction, because metastin mediate the preovulatory LH release in the rats. The recent results imply that suppression of pulsatile release of LH in lactating rats is mainly due to the inhibition of metastin expression in the brain.