Bailey A R, Honda K, Smith R G, Leng G
Department of Biomedical Sciences, University Medical School, Edinburgh, UK.
Neuroendocrinology. 1999 Aug;70(2):101-6. doi: 10.1159/000054464.
Growth hormone secretagogues (GHS) administered systemically selectively induce growth hormone (GH) release from the pituitary and the expression of Fos protein in arcuate nucleus neurons. Both the control of GH release and the expression of the GHS receptor in the arcuate nucleus are thought to be regulated, at least in part, by the negative feedback actions of GH. In this study, we utilized the immunocytochemical detection of Fos protein to examine the effects of morphine- and GH-releasing hormone (GHRH)-induced GH release on the activation of arcuate nucleus neurons following GHS administration. Given alone, two structurally different GHS induced significant amounts of Fos-LI in the arcuate nucleus of male rats, suggesting activation of cells in this region. Prior administration of morphine or GHRH significantly reduced the number of Fos-positive cells in the arcuate nucleus of rats injected with either GHS, although when given together, morphine and GHRH did not produce a greater reduction in Fos expression than when given alone. In no case was there a complete reduction in Fos expression, indicating that some arcuate nucleus neurons are not subject to the feedback effects of endogenous GH. These results provide evidence that, in the male rat, GH can feedback to the hypothalamus, altering the responsiveness of neurons involved in the central response to GHS.
全身给药的生长激素促分泌素(GHS)可选择性地诱导垂体释放生长激素(GH),并诱导弓状核神经元中Fos蛋白的表达。人们认为,至少部分地,弓状核中GH释放的控制和GHS受体的表达受GH的负反馈作用调节。在本研究中,我们利用Fos蛋白的免疫细胞化学检测,来研究吗啡和生长激素释放激素(GHRH)诱导的GH释放对给予GHS后弓状核神经元激活的影响。单独给予时,两种结构不同的GHS均可在雄性大鼠的弓状核中诱导大量Fos样免疫反应(Fos-LI),提示该区域细胞被激活。预先给予吗啡或GHRH可显著减少注射GHS的大鼠弓状核中Fos阳性细胞的数量,不过,吗啡和GHRH联合给予时,Fos表达的降低幅度并不比单独给予时更大。在任何情况下,Fos表达均未完全降低,这表明一些弓状核神经元不受内源性GH的反馈作用影响。这些结果提供了证据,表明在雄性大鼠中,GH可反馈至下丘脑,改变参与对GHS的中枢反应的神经元的反应性。