Brain mechanism by which estrogen enhances fasting-induced suppression of reproductive function

禁食应激以雌激素依赖的方式深刻地抑制大鼠黄体生成素(LH)的分泌。结果表明，禁食48h后，下丘脑室旁核(PVN)和下部脑干孤束核(NTS)A2区雌激素受体阳性细胞数明显增加。本研究旨在探讨雌激素增强禁食诱导的促黄体生成素分泌抑制作用的脑机制。本研究观察了禁食和药物干预对去卵巢大鼠下丘脑室旁核和孤束核内雌激素受体α(ER-α)阳性细胞数量的影响。此外，还确定了孤束核和下丘脑室旁核A2区酪氨酸羟化酶(TH)和多巴胺α羟化酶(DBH)阳性神经元内ERβ免疫反应的解剖学关系。禁食30h后，下丘脑室旁核和腹侧核ERα-ir细胞数较禁食对照组显著增加，并持续至48h，糖化疗法也使这些核团内ERα-ir细胞数显著增加。禁食48h和葡萄糖灌胃显著增加含ER-α的TH/DBH-ir细胞。在下丘脑室旁核内，多数ERα阳性神经元与TH和DbH阳性神经元并列分布。这些结果表明，从禁食开始，ERα在特定的脑区表达，葡萄糖利用率的降低可能是介导禁食诱导的ERα表达变化的关键信号。此外，A2区去甲肾上腺素能神经元和下丘脑室旁核内ERα-ir神经元的解剖关系可能提示雌激素在增强A2区去甲肾上腺素能神经元的活性和增强室旁核对来自下脑干的去甲肾上腺素能输入的敏感性，从而加强禁食时对黄体生成素分泌的抑制。

Fasting-stress profoundly suppresses luteinizing hormone (LH) secretion in the rat in an estrogen dependent manner. It has been demonstrated that 48-h fasting significantly increased numbers of estrogen receptor-containing cells in both the hypothalamic paraventricular nucleus (PVN) and A2 region of solitary tract nucleus (NTS) in the lower brain stem. The present research aimed to investigate the brain mechanism by which estrogen enhances fasting-induced suppression of LH secretion.Changes in the number of estrogen receptor α (ERα) -containing cells by fasting and pharmacological glucoprivation were investigated in the PVN and NTS of ovariectomized rats. It has been also determined that the anatomical relationship of ERα immunoreactivity within tyrosine hydroxylase (TH) -and dopamine-β-hydroxylase (DBH) -ir neurons in the A2 region of the NTS and the PVN. The number of ERα-ir cells significantly increased after 30 h from the onset of fasting in the PVN and NTS compared with the unfasted controls and was sustained until 48 h. Glucoprivation also significantly increased the number of ERα-ir cells in these nuclei. Forty-eight h fasting and glucoprivation significantly increased ERα-containing TH-/DBH-ir cells. In the PVN, most ERα-ir neurons were juxtaposed with TH-and DBH-ir varicosities. These results suggest that ERα is expressed in specific brain regions at a defined time from the onset of fasting, and that lowered glucose utilization might be the key signal mediating this fasting-induced changes in ERα expression. In addition, the anatomical relationship of noradrenergic and ERα-ir neurons in the A2 region and PVN may suggest a role for estrogen in increasing the activity of noradrenergic neurons in the A2 region and the sensitivity of the PVN to noradrenergic input arising from the lower brainstem and thereby augmenting the suppression of LH secretion during fasting.