Barker-Gibb M L, Clarke I J
Prince Henry's Institute of Medical Research, Clayton, Vic., Australia.
Neuroendocrinology. 1996 Sep;64(3):194-207. doi: 10.1159/000127118.
Manipulation of diet is known to affect the secretion of the gonadotropins and growth hormone (GH). The former are under the direct regulation of hypothalamic gonadotropin-releasing hormone (GnRH) and the latter is under the dual control of GH-releasing hormone (GHRH) and somatostatin (SRIH). At the level of the hypothalamus, both galanin (GAL) and neuropeptide Y (NPY) are thought to regulate the secretion of the above releasing and inhibiting factors. Both peptides are also potent orexigenic agents. We have studied ovariectomised ewes that were either well-fed (HIGHs) or underfed (LOWs) and used immunocytochemistry and image analysis to measure the levels of GAL and NPY in hypothalamic nuclei in which GnRH, GHRH and SRIH are found and which are also involved in the regulation of appetite and feeding. The sheep were given a normal diet or a restricted diet for 15 months. Four pairs of ewes were then blood-sampled to measure GH, luteinising hormone (LH), and follicle-stimulating hormone (FSH) and then killed for recovery of the brains. After perfusion, cryostat sections were cut through the entire hypothalamus, mounted, and stained fro NPY or GAL. All treatments and analyses were performed in pairs. The number of immunoreactive cells, density of terminals and total immunoreactivity (IR) were quantified by image analysis by sampling 6-16 subareas (depending on region) on sections through the pre-optic area (POA), paraventricular nucleus (PVN), arcuate nucleus (ARC) and median eminence (ME). Mean (+/- SEM) live weight of the LOWs was significantly (p < 0.0001) lower than that of the HIGHs (37.6 +/- 0.6 kg vs. 60.6 +/- 0.5 kg). There was no difference in the plasma levels of LH and FSH but the area under the GH curve (ng/ml/h) was significantly (p < 0.0001) greater in the LOWs (320 +/- 40.9 vs. 67.3 +/- 16.1). There was an increased number of cells staining for NPY but not GAL in the ARC/ME of the LOWs. Nevertheless, the oveall level of immunostaining for both peptides was increased in the LOWs. GAL IR was restricted to the mediobasal hypothalamus. In the LOWs, the density of NPY terminal fields in each area of the ARC was significantly (p < 0.05) increased. Food restriction also increased the density of NPY terminals in the POA and PVN (p < 0.025) but not in the ME. These data indicate that a dietary manipulation which affects GH secretion but not the gonadotropins may be mediated by NPY and GAL neuronal systems in specific brain regions within the hypothalamus.
众所周知，饮食调控会影响促性腺激素和生长激素（GH）的分泌。前者受下丘脑促性腺激素释放激素（GnRH）的直接调控，而后者受生长激素释放激素（GHRH）和生长抑素（SRIH）的双重控制。在下丘脑水平，甘丙肽（GAL）和神经肽Y（NPY）均被认为可调节上述释放因子和抑制因子的分泌。这两种肽也是强效的食欲促进剂。我们研究了喂食良好（HIGHs）或喂食不足（LOWs）的去卵巢母羊，并使用免疫细胞化学和图像分析来测量下丘脑核团中GAL和NPY的水平，这些核团中存在GnRH、GHRH和SRIH，并且也参与食欲和进食的调节。给这些绵羊提供正常饮食或限制饮食15个月。然后对四对母羊进行采血以测量GH、黄体生成素（LH）和卵泡刺激素（FSH），随后将其处死以取出大脑。灌注后，将整个下丘脑切成低温恒温切片，固定并进行NPY或GAL染色。所有处理和分析均成对进行。通过图像分析对免疫反应性细胞数量、终末密度和总免疫反应性（IR）进行定量，在通过视前区（POA）、室旁核（PVN）、弓状核（ARC）和正中隆起（ME）的切片上对6 - 16个亚区域（取决于区域）进行采样。LOWs的平均（±SEM）活体重显著低于HIGHs（p < 0.0001）（37.6 ± 0.6 kg对60.6 ± 0.5 kg）。LH和FSH的血浆水平没有差异，但LOWs中GH曲线下面积（ng/ml/h）显著更大（p < 0.0001）（320 ± 40.9对67.3 ± 16.1）。在LOWs的ARC/ME中，NPY染色的细胞数量增加，但GAL染色的细胞数量未增加。然而，在LOWs中这两种肽的总体免疫染色水平均升高。GAL IR局限于下丘脑内侧基底部。在LOWs中，ARC每个区域的NPY终末场密度显著增加（p < 0.05）。食物限制也增加了POA和PVN中NPY终末的密度（p < 0.025），但ME中未增加。这些数据表明，一种影响GH分泌但不影响促性腺激素的饮食调控可能由下丘脑特定脑区中的NPY和GAL神经元系统介导。
