Reduction of luteinzing hormone secretion induced by long-term feed restriction in male rats is associated with increased expression of GABA-synthesizing enzymes without alterations of GnRH gene expression

In rats, fasting or restriction of feed intake impairs the activity of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse-generator which re sults in reduced luteinizing hormone (LH) secretion. It is still unknown wh ich neurotransmitters are involved in this phenomenon, However, it is known that increased GABA concentrations in the hypothalamus reduce GnRH biosynt hesis and release. Therefore, we examined whether 17 days of feed restricti on in male rats affected the hypothalamic gene expression of GnRH and the G ABA-synthesizing enzymes glutaminase (GLS) and glutamic acid decarboxylase- which exists in two forms, GAD67 and GAD65-in the mammalian brain. Furtherm ore, the expression of the GnRH receptor (GnRH-R) and the GABA transporter 1 (GAT-1) were investigated. Feed restriction resulted in a 75% reduction i n body weight (b.w,) compared to rats fed ad libitum. Serum concentrations of LH and testosterone in the feed restricted group were significantly redu ced to approximate to 15% of that of rats fed ad libitum, while the FSH con centration remained unchanged, In the mediobasal hypothalamus (MBH) where G nRH 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 obs erved in the preoptic area of the hypothalamus (POA) where GnRH is biosynth esised. Neither the expression of preoptic GnRH mRNA nor the expression of GAD65 and of GnRH-R mRNA in both hypothalamic structures was affected by fe ed restriction. In the anterior pituitary, a significant reduction of the e xpression of GnRH-R, LH-beta and the alpha subunit was observed in the feed restricted rats, whereas FSH-P mRNA levels remained constant. Thus, feed r estriction selectively increased the expression of GABA-synthesizing enzyme s in the MBH but did not modify GnRH expression in the POA, However, the re duced 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 att enuated or even abolished. We suggest, that enhanced expression of GABA-syn thesizing enzymes reflects increased GABAergic neurotransmission and thereb y reducing GnRH release from the MBH.