Differential effect of baclofen on hypothalamic GnRH and pituitary LH beta gene expression in steroid-treated rats.
gamma-Aminobutyric acid (GABA) is known to be a major inhibitory neurotransmitter in the brain. The present study was performed to elucidate the possibility of differential roles of baclofen, a GABAB receptor agonist, in gonadotropin releasing hormone (GnRH) and luteinizing hormone beta (LH beta) subunit gene expression. To examine the effect of baclofen on GnRH gene expression in the hypothalamus, it was subcutaneously administered to ovariectomized (OVX) and 17 beta-estradiol (E) and progesterone (P)-treated rats. Baclofen (2 mg) enhanced the GnRH mRNA level and this stimulatory action of baclofen was also confirmed by intracerebroventricular injection of baclofen (2 micrograms). To examine the effect of GABA on LH beta gene expression in the pituitary, the OVX + E-treated model was used rather than the OVX + E + P-treated model because the stimulatory action of baclofen overlapped with that of P. Baclofen (2 mg) was administered subcutaneously to OVX + E-treated rats 48 h after E implants and animals were sacrificed 6 h after administration of baclofen. Baclofen further decreased the LH beta mRNA level which had already been decreased by E, but had no effect on the prolactin mRNA level. The inhibitory effect of baclofen on the LH beta mRNA level lasted at least for 6 h following treatment. The release of LH was decreased by baclofen in the presence of E. The action site of GABA in LH beta subunit gene expression seems to be different from that of P, because the restoration of LH beta mRNA level with RU486 was not suppressed by baclofen. This study suggests that activation of GABAB receptor with baclofen may play differential roles in regulating hypothalamic GnRH and pituitary LH beta gene expression depending on steroid milieu.
Cho
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Department of Molecular Biology, College of Natural Sciences, Seoul National University, Korea.
Kim
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K
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000187:drug effects / Q000235:genetics*; D015735:Mifepristone / Q000494:pharmacology; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors
D012333:RNA, Messenger; D011980:Receptors, Progesterone; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D001418:Baclofen