Kang S S, Son G H, Seong J Y, Choi D, Kwon H B, Lee C C, Kim K
Department of Molecular Biology and Research Centre for Cell Differentiation, College of Natural Sciences, Seoul National University, Korea.
J Neuroendocrinol. 1998 Dec;10(12):911-8. doi: 10.1046/j.1365-2826.1998.00278.x.
The present study was designed to investigate whether noradrenergic neurotransmission regulates the gene expression of gonadotropin-releasing hormone (GnRH) in the preoptic area and GnRH receptor in the pituitary. To this end, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4, 50 mg/kg), an intraperitoneal (i.p.) injection of selective noradrenergic neurotoxin, was administered 1 h before progesterone (1 mg) treatment in ovariectomized and estradiol-treated prepubertal rats. Treatment with DSP4 effectively blocked the progesterone-induced increase in hypothalamic noradrenaline content, but not dopamine content, indicating that DSP4 selectively inhibits noradrenergic neurotransmission. DSP4 significantly blocked progesterone-induced increase in serum luteinizing hormone (LH) concentrations as well as GnRH release from hypothalamic fragments incubated in vitro. DSP4 concomitantly down-regulated GnRH mRNA levels in the preoptic area, as determined by competitive reverse transcription-polymerase chain reaction. DSP4 also clearly down-regulated progesterone-induced GnRH receptor mRNA levels in the pituitary, whereas it failed to alter LHbeta mRNA levels. In summary, blockade of noradrenergic neurotransmission with DSP4 resulted in profound reductions of hypothalamic GnRH and pituitary GnRH receptor gene expression.
本研究旨在调查去甲肾上腺素能神经传递是否调节视前区促性腺激素释放激素（GnRH）的基因表达以及垂体中GnRH受体的基因表达。为此，在去卵巢并经雌二醇处理的青春期前大鼠中，于孕酮（1mg）处理前1小时腹腔注射选择性去甲肾上腺素能神经毒素N-（2-氯乙基）-N-乙基-2-溴苄胺（DSP4，50mg/kg）。DSP4处理有效地阻断了孕酮诱导的下丘脑去甲肾上腺素含量的增加，但未阻断多巴胺含量的增加，表明DSP4选择性抑制去甲肾上腺素能神经传递。DSP4显著阻断了孕酮诱导的血清黄体生成素（LH）浓度的增加以及体外培养的下丘脑片段中GnRH的释放。通过竞争性逆转录-聚合酶链反应测定，DSP4同时下调了视前区GnRH mRNA水平。DSP4还明显下调了孕酮诱导的垂体中GnRH受体mRNA水平，而未能改变LHβ mRNA水平。总之，用DSP4阻断去甲肾上腺素能神经传递导致下丘脑GnRH和垂体GnRH受体基因表达显著降低。
