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Departments of Pathology, Cell Biology and Anatomy, and Neurology (S.J.K., T.W.A., N.E.R.), University of Arizona College of Medicine, Tucson, Arizona 85724; and Department of Pathology, Section of Comparative Medicine (M.L.V.), Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157
Address all correspondence and requests for reprints to: Naomi E. Rance, M.D., Ph.D., Department of Pathology, University of Arizona College of Medicine, 1501 North Campbell Avenue, Tucson, Arizona 85724. E-mail: nrance{at}u.arizona.edu.
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.
Present address for T.W.A.: Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland.
This work was supported by NIH/National Institute on Aging Grant AG-09214.
Abbreviations: OVX, Ovariectomized controls; OVX + E, continuous estrogen treatment; OVX + EP, estrogen plus progesterone treatment.
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