Effect of interleukin-1 beta on gonadotropin-releasing hormone (GnRH) and GnRH receptor gene expression in castrated male rats

Increasing evidence suggests that interleukin-1 beta (IL-1 beta) regulates luteinizing hormone (LH) release primarily through modulation of the gonado tropin-releasing hormone (GnRH) neuronal activity. This study was undertake n to elucidate the effect of IL-1 beta on GnRH as well as GnRH receptor (Gn RHR) gene expression in the preoptic area. IL-1 beta (100 ng/rat) or saline was administered into the lateral ventricle of castrated rats. RNA samples were isolated from micropunches of the preoptic area and mediobasal hypoth alamus from individual brain slices and GnRH mRNA levels in the preoptic ar ea and GnRHR mRNA levels in the mediobasal hypothalamus were determined by competitive reverse transcription-polymerase chain reaction (RT-PCR) protoc ols. Serum LH concentrations were decreased from 1 h to 3 h after IL-1 beta treatment, but rebounded at 5 h, while serum concentrations of follicle-st imulating hormone (FSH) and prolactin were not altered. There were no signi ficant changes in GnRH mRNA levels from the micropunched preoptic area, whi le GnRHR mRNA levels from the preoptic area and mediobasal hypothalamus mic ropunch samples, but not in the anterior pituitary, showed a pattern simila r to the serum LH profile following i.c.v. administration of IL-1 beta. We then examined the effect of IL-1 beta on the translational efficiency of th e GnRH mRNA. After the separation and fractionation of polyribosome-associa ted cytoplasmic RNA from the hypothalamic fragments containing the preoptic area-anterior hypothalamic area of control (saline-treated) and IL-1 beta- treated group 3 h after administration, GnRH transcript levels were examine d from the each fraction. IL-1 beta decreased the translational efficiency of the transcribed GnRH mRNA. These results clearly demonstrate that centra l administration of IL-1 beta suppresses the translational activity of GnRH mRNA. Moreover, GnRHR may play an important role in the modulation of GnRH neuronal activity through GnRHR-expressing neurones (or glia) in the hypot halamus.