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KMID : 0578319970070050605
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Molecules and Cells
1997 Volume.7 No. 5 p.605 ~ p.609
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Differential Effect of Baclofen on Hypothalmic GnRH and Pituitary LHβ Gene Expression in Steroid-treated Rats
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Cho Byung-Nam
Kim Kyung-Jin
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Abstract
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γ-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 GABA_(g) receptor agonist, in gonadotropin releasing hormone (GnRH) and luteinizing hormone β (LHβ) subunit gene expression. To examine the effect of baclofen on GnRH gene expression in the hypothalamus, it was subcutaneously administered to ovariectomized (OVX) and 17β-estradiol (E) and progresterone (P)-treated rats. Baclofen (2 mg) enhanced the GnRH mRNA level and this stimulatory action of baclofen was also confirmed by intracebroventricular injection of baclofen (2 ㎍). To examine the effect of GABA on LHβ 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 LHβ 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 LHβ mRNA level lasted for 6 h following treatment. The release of LH was decreased by baclofen in the presence of E. The action site of GABA in LHβ subunit gene expression seems to be different from that of P, because the restoration of LHβ mRNA level with RU486 was not suppressed by baclofen. This study suggests that activation of GABA_(B) receptor with baclofen may play differential roles in regulating hypothalamin GnRH and pituitary LHβ gene expression depending on steroid milieu.
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KEYWORD
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