Interaction between GABA and norepinephrine in interleukin-1beta-induced suppression of the luteinizing hormone surge.
Interleukin-1beta (IL-1beta), a cytokine that is closely associated with inflammation and immune stress, is known to interfere with reproductive functions. Earlier studies have demonstrated that IL-1beta inhibits the luteinizing hormone (LH) surge during the afternoon of proestrus in female rats. We have shown that this effect is most probably mediated through a reduction in norepinephrine (NE) levels in the medial preoptic area (MPA) of the hypothalamus. However, the mechanism by which IL-1beta decreases NE levels in the MPA is unclear. We hypothesized that the inhibitory neurotransmitter, GABA could play a role in decreasing NE levels in the MPA. To test this, ovariectomized, steroid-primed rats were injected (i.p.) with either PBS-BSA (control) or 5 microg of IL-1beta, alone or in combination with i.c.v. administration of GABA-A and GABA-B receptor antagonists, Bicuculline and CGP 35348 (CGP) respectively. Animals were subjected to push-pull perfusion of the MPA and perfusates collected at 30 min intervals were analyzed for both NE and GABA levels using HPLC-EC. Simultaneously, serial plasma samples were obtained through jugular catheters and were analyzed for LH levels using RIA. Compared to control rats, NE levels decreased significantly in the MPA in IL-1beta-treated rats (p<0.05). Concurrently, there was a significant increase in GABA levels in the MPA (p<0.05). The GABA-A receptor antagonist, bicuculline, was able to reverse the effect of IL-1beta on NE and LH, while the GABA-B receptor antagonist, CGP 35348 was without any effect. This leads us to conclude that the IL-1beta-induced suppression of the LH surge is most probably mediated through an increase in GABA levels in the MPA which causes a reduction in NE levels. This is probably one of the mechanisms by which IL-1beta inhibits reproductive functions.
Sirivelu
Madhu P
MP
Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, E. Lansing, MI 48824, USA.
Burnett
Robert
R
Shin
Andrew C
AC
Kim
Charlotte
C
MohanKumar
P S
PS
MohanKumar
Sheba M J
SM
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002405:Catheterization, Central Venous; D002851:Chromatography, High Pressure Liquid; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D053583:Interleukin-1beta / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood*; D009638:Norepinephrine / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011301:Preoptic Area / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D053583:Interleukin-1beta; D009943:Organophosphorus Compounds; D011374:Progesterone; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D007986:Luteinizing Hormone; D009638:Norepinephrine; D001640:Bicuculline