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对生殖抑制的机制。我们以前已经表明，禁食抑制黄体生成素（LH）的脉冲释放在一个雌激素依赖的方式在大鼠。我们还报道了下丘脑室旁核（PVN）是一个雌激素作用部位，参与空腹诱导的LH抑制，空腹和葡萄糖活化诱导PVN中雌激素受体a （ERa）的表达。本研究表明，空腹和糖糖化诱导的PVN中ERa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，本研究表明，在营养不良时，向终纹床核（BNST）投射的去甲肾上腺素能神经元可能介导了LH分泌的抑制。结果表明，作为生殖活性指标的多单位活性（MUA）受到禁食的抑制。我们还在山羊身上发现了黑素皮质素系统参与生殖能量调节的可能性。最后，本研究发现，matastin是一种新型神经肽，是GPR54的天然配体，在大鼠的生殖调节中起着核心作用，因为matastin介导了大鼠排卵前LH的释放。最近的研究结果表明，抑制泌乳大鼠脉搏性LH释放主要是由于抑制脑内转移蛋白的表达。

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.