Ovarian steroids differentially modulate the gene expression of gonadotropin-releasing hormone neuronal subtypes in the ovariectomized cynomolgus monkey.

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.