Leonhardt S, Shahab M, Luft H, Wuttke W, Jarry H
Division of Clinical and Experimental Endocrinology, Department of Obstetrics and Gynecology, University of Göttingen, Germany.
J Neuroendocrinol. 1999 Aug;11(8):613-9. doi: 10.1046/j.1365-2826.1999.00377.x.
In rats, fasting or restriction of feed intake impairs the activity of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator which results in reduced luteinizing hormone (LH) secretion. It is still unknown which neurotransmitters are involved in this phenomenon. However, it is known that increased GABA concentrations in the hypothalamus reduce GnRH biosynthesis and release. Therefore, we examined whether 17 days of feed restriction in male rats affected the hypothalamic gene expression of GnRH and the GABA-synthesizing enzymes glutaminase (GLS) and glutamic acid decarboxylase-which exists in two forms, GAD67 and GAD65-in the mammalian brain. Furthermore, the expression of the GnRH receptor (GnRH-R) and the GABA transporter 1 (GAT-1) were investigated. Feed restriction resulted in a 75% reduction in body weight (b.w.) compared to rats fed ad libitum. Serum concentrations of LH and testosterone in the feed restricted group were significantly reduced to approximately 15% of that of rats fed ad libitum, while the FSH concentration remained unchanged. In the mediobasal hypothalamus (MBH) where GnRH is released into the portal vessels, mRNA levels of GAD67 and GLS were increased twofold compared to rats fed ad libitum while no changes were observed in the preoptic area of the hypothalamus (POA) where GnRH is biosynthesised. Neither the expression of preoptic GnRH mRNA nor the expression of GAD65 and of GnRH-R mRNA in both hypothalamic structures was affected by feed restriction. In the anterior pituitary, a significant reduction of the expression of GnRH-R, LH-beta and the alpha subunit was observed in the feed restricted rats, whereas FSH-beta mRNA levels remained constant. Thus, feed restriction selectively increased the expression of GABA-synthesizing enzymes in the MBH but did not modify GnRH expression in the POA. However, the reduced expression of the LH-beta- and alpha-subunit and of the GnRH-R in the anterior pituitary indicates that pulsatile GnRH release may have been attenuated or even abolished. We suggest, that enhanced expression of GABA-synthesizing enzymes reflects increased GABAergic neurotransmission and thereby reducing GnRH release from the MBH.
在大鼠中，禁食或限制饲料摄入量会损害下丘脑促性腺激素释放激素（GnRH）脉冲发生器的活性，从而导致黄体生成素（LH）分泌减少。目前仍不清楚哪些神经递质参与了这一现象。然而，已知下丘脑γ-氨基丁酸（GABA）浓度升高会降低GnRH的生物合成和释放。因此，我们研究了雄性大鼠17天的饲料限制是否会影响下丘脑GnRH以及GABA合成酶谷氨酰胺酶（GLS）和谷氨酸脱羧酶（存在两种形式，即GAD67和GAD65）在哺乳动物大脑中的基因表达。此外，还研究了GnRH受体（GnRH-R）和GABA转运体1（GAT-1）的表达。与自由采食的大鼠相比，饲料限制导致体重下降了75%。饲料限制组的血清LH和睾酮浓度显著降低至自由采食大鼠的约15%，而促卵泡激素（FSH）浓度保持不变。在GnRH释放到门静脉的中基底下丘脑（MBH）中，与自由采食的大鼠相比，GAD67和GLS的mRNA水平增加了两倍，而在GnRH生物合成的下丘脑视前区（POA）未观察到变化。饲料限制对两个下丘脑结构中视前区GnRH mRNA的表达以及GAD65和GnRH-R mRNA的表达均无影响。在垂体前叶，饲料限制的大鼠中GnRH-R、LH-β和α亚基的表达显著降低，而FSH-β mRNA水平保持不变。因此，饲料限制选择性地增加了MBH中GABA合成酶的表达，但未改变POA中GnRH的表达。然而，垂体前叶中LH-β和α亚基以及GnRH-R的表达降低表明GnRH的脉冲式释放可能已经减弱甚至消失。我们认为，GABA合成酶表达的增强反映了GABA能神经传递的增加，从而减少了GnRH从MBH的释放。
