Krajewski Sally J, Abel Ty W, Voytko Mary Lou, Rance Naomi E
Department of Pathology, University of Arizona College of Medicine, Tucson, Arizona 85724, USA.
J Clin Endocrinol Metab. 2003 Feb;88(2):655-62. doi: 10.1210/jc.2002-020887.
In the present study, we compared the morphology and distribution of neurons expressing GnRH gene transcripts in the hypothalamus and forebrain of the cynomolgus monkey to that of the human. As in the human, three subtypes of GnRH neurons were identified. Type I GnRH neurons were small, oval cells with high levels of gene expression and were located within the basal hypothalamus. Type II GnRH neurons were small and sparsely labeled and were widely scattered in the hypothalamus, midline nuclei of the thalamus, and extended amygdala. Type III neurons displayed magnocellular morphology and intermediate labeling intensity and were located in the nucleus basalis of Meynert, caudate, and amygdala. In a second experiment, we determined the effect of estrogen or estrogen plus progesterone on the gene expression of GnRH neurons in the brains of young, ovariectomized cynomolgus monkeys. We report that hormone treatment resulted in a significant decrease in GnRH mRNA in type I neurons within the basal hypothalamus of ovariectomized monkeys. In contrast, there was no effect of hormone treatment on the gene expression of type III GnRH neurons in the nucleus basalis of Meynert. The present findings provide evidence that the increase in gene expression of type I GnRH neurons in postmenopausal women is secondary to the ovarian failure of menopause. The differential responses of type I and III GnRH neurons to hormone treatment provide additional evidence that distinct subpopulations of neurons expressing GnRH mRNA exist in the primate hypothalamus.
在本研究中，我们比较了食蟹猴下丘脑和前脑与人类中表达促性腺激素释放激素（GnRH）基因转录本的神经元的形态和分布。与人类一样，GnRH神经元被鉴定出三种亚型。I型GnRH神经元是小的椭圆形细胞，基因表达水平高，位于下丘脑基部。II型GnRH神经元小且标记稀疏，广泛分布于下丘脑、丘脑中线核和延伸杏仁核。III型神经元呈现大细胞形态和中等标记强度，位于迈内特基底核、尾状核和杏仁核。在第二个实验中，我们确定了雌激素或雌激素加孕酮对年轻的、卵巢切除的食蟹猴大脑中GnRH神经元基因表达的影响。我们报告称，激素治疗导致卵巢切除的猴子下丘脑基部I型神经元中GnRH mRNA显著减少。相比之下，激素治疗对迈内特基底核中III型GnRH神经元的基因表达没有影响。目前的研究结果提供了证据，表明绝经后女性I型GnRH神经元基因表达的增加是绝经后卵巢功能衰竭的继发结果。I型和III型GnRH神经元对激素治疗的不同反应提供了额外的证据，表明灵长类动物下丘脑存在表达GnRH mRNA的不同神经元亚群。
