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 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.
Leonhardt
S
S
Division of Clinical and Experimental Endocrinology, Department of Obstetrics and Gynecology, University of Göttingen, Germany.
Shahab
M
M
Luft
H
H
Wuttke
W
W
Jarry
H
H
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D005508:Food Deprivation; D050485:GABA Plasma Membrane Transport Proteins; D015870:Gene Expression; D005968:Glutamate Decarboxylase / Q000235:genetics; D005972:Glutaminase / Q000235:genetics; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D007033:Hypothalamus, Middle / Q000201:enzymology; D007986:Luteinizing Hormone / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D011301:Preoptic Area / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013739:Testosterone / Q000097:blood; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D015292:Glycoprotein Hormones, alpha Subunit; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C493415:Slc6a1 protein, rat; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D005680:gamma-Aminobutyric Acid; D007986:Luteinizing Hormone; D005972:Glutaminase; D005968:Glutamate Decarboxylase