Tannenbaum G S, Epelbaum J, Videau C, Dubuis J M
Department of Pediatrics, McGill University, Québec, Canada.
Neuroendocrinology. 1996 Sep;64(3):186-93. doi: 10.1159/000127117.
The possibility that the growth hormone (GH) suppression associated with obesity is due to alterations in hypothalamic GH-releasing hormone (GHRH) and/or somatostatin (SRIH) has been considered, but the data are not consistent. In the present study, we sought to clarify the roles of GHRH and SRIH in obesity by using in situ hybridization to localize and quantify the level of expression of GHRH mRNA- and SRIH mRNA-containing neurons in the hypothalamus of male and female lean and obese Zucker rats (12 weeks of age; n = 6 per group). In lean animals, the number of GHRH mRNA-expressing cells in the arcuate nucleus and SRIH mRNA-containing neurons in the periventricular nucleus was 2- to 3-fold higher in males compared to females. The obese phenotype in the male was associated with a striking reduction in arcuate GHRH mRNA expression, both in terms of number of cells (-71%; p < 0.01) and grains/cell (-44%; p < 0.05). In contrast, in obese females, there was a marked augmentation (+ 175%; p < 0.05) in the number of GHRH mRNA-containing cells in the arcuate nucleus compared to their lean littermates. The small population of GHRH mRNA-containing neurons of the ventromedial nucleus was not modified in male obese rats, while it was considerably increased (p < 0.05) in obese females. Neither the number of labeling density of SRIH mRNA-containing neurons in the periventricular and arcuate nuclei of obese rats of either sex was changed when compared to their sex-matched lean counterparts. These results demonstrate that: (1) the obese male Zucker rat exhibits a marked diminution in hypothalamic GHRH mRNA expression, while a reverse pattern is evident in the obese female; (2) hypothalamic SRIH mRNA-containing neurons are not significantly altered in obese rats of both sexes. Our findings suggest that the impaired GH secretion of the obese Zucker rat is due, at least in part, to alterations in hypothalamic GHRH gene expression and that SRIH does not play a major role.
肥胖相关的生长激素（GH）抑制现象是否归因于下丘脑生长激素释放激素（GHRH）和/或生长抑素（SRIH）的改变，这一问题已受到关注，但相关数据并不一致。在本研究中，我们通过原位杂交技术，对雄性和雌性瘦型及肥胖型 Zucker 大鼠（12 周龄；每组 n = 6）下丘脑内含有 GHRH mRNA 和 SRIH mRNA 的神经元进行定位和定量表达水平分析，以阐明 GHRH 和 SRIH 在肥胖中的作用。在瘦型动物中，雄性大鼠弓状核中表达 GHRH mRNA 的细胞数量以及室周核中含有 SRIH mRNA 的神经元数量比雌性大鼠高 2 至 3 倍。雄性肥胖表型与弓状核 GHRH mRNA 表达显著降低有关，无论是细胞数量（-71%；p < 0.01）还是每个细胞的颗粒数（-44%；p < 0.05）。相比之下，肥胖雌性大鼠弓状核中含有 GHRH mRNA 的细胞数量比其瘦型同窝仔鼠显著增加（+ 175%；p < 0.05）。腹内侧核中少量含有 GHRH mRNA 的神经元在雄性肥胖大鼠中未发生改变，而在肥胖雌性大鼠中则显著增加（p < 0.05）。与性别匹配的瘦型大鼠相比，无论雌雄，肥胖大鼠室周核和弓状核中含有 SRIH mRNA 的神经元标记密度数量均未改变。这些结果表明：（1）肥胖雄性 Zucker 大鼠下丘脑 GHRH mRNA 表达显著减少，而肥胖雌性大鼠则呈现相反模式；（2）肥胖大鼠两性下丘脑内含有 SRIH mRNA 的神经元均无显著改变。我们的研究结果表明，肥胖 Zucker 大鼠生长激素分泌受损至少部分归因于下丘脑 GHRH 基因表达的改变，而 SRIH 并未发挥主要作用。
