Ghosh P K, Debeljuk L, Wagner T E, Bartke A
Department of Physiology, School of Medicine, Southern Illinois University, Carbondale 62901.
Endocrinology. 1991 Aug;129(2):597-602. doi: 10.1210/endo-129-2-597.
Immunoneutralization of endogenous neuropeptide Y (NPY) with specific antibodies was used to evaluate the possible physiological role of this neuropeptide in the regulation of gonadotropin and PRL secretion in the mouse. Because regulation of anterior pituitary function can be profoundly altered by chronic GH excess, we felt it was also of interest to have examined the effects of immunoneutralization of NPY in transgenic mice expressing bovine (b) GH gene with mouse metallothionein-I promotor. Intact or castrated transgenic and normal (nontransgenic) littermate adult male mice were injected with control rabbit serum or anti-NPY rabbit serum (anti-NPY). Blood samples were obtained 24 h later for hormone measurements. In intact transgenic mice expressing bGH gene, plasma LH levels were reduced and plasma PRL levels were increased, as compared to their normal littermates. Plasma levels of FSH were similar in normal and transgenic animals. Injection of anti-NPY increased plasma LH levels significantly in both intact normal and intact transgenic mice. However, plasma levels of FSH and PRL were increased significantly after anti-NPY treatment only in intact normal mice. In both normal and transgenic males, castration lead to the expected increase in plasma FSH and LH levels, whereas plasma levels of PRL remained unaltered. Administration of anti-NPY to castrated animals was followed by a significant increase in circulating LH levels in both transgenic and normal mice, whereas plasma levels of PRL were not changed. The results suggest that NPY plays a physiological role in the control of gonadotropin and PRL release in the adult male mouse, and that expression of the bGH gene in transgenic mice is associated with altered role of endogenous NPY in the control of pituitary function.
用特异性抗体对内源性神经肽Y(NPY)进行免疫中和,以评估该神经肽在调节小鼠促性腺激素和催乳素分泌中的可能生理作用。由于慢性生长激素过量会深刻改变垂体前叶功能的调节,我们认为研究用小鼠金属硫蛋白-I启动子表达牛(b)生长激素基因的转基因小鼠中NPY免疫中和的作用也很有意义。完整或阉割的转基因成年雄性小鼠和正常(非转基因)同窝成年雄性小鼠分别注射对照兔血清或抗NPY兔血清(抗NPY)。24小时后采集血样进行激素测定。与正常同窝小鼠相比,表达bGH基因的完整转基因小鼠血浆LH水平降低,血浆PRL水平升高。正常和转基因动物的血浆FSH水平相似。在完整的正常小鼠和完整的转基因小鼠中,注射抗NPY均显著提高了血浆LH水平。然而,仅在完整的正常小鼠中,抗NPY处理后血浆FSH和PRL水平显著升高。在正常和转基因雄性小鼠中,阉割均导致血浆FSH和LH水平预期升高,而血浆PRL水平保持不变。给阉割动物注射抗NPY后,转基因小鼠和正常小鼠的循环LH水平均显著升高,而血浆PRL水平未改变。结果表明,NPY在成年雄性小鼠促性腺激素和PRL释放的控制中发挥生理作用,并且转基因小鼠中bGH基因的表达与内源性NPY在垂体功能控制中的作用改变有关。