Our primary goal is to learn about the basic neuroendocrine mechanisms controlling the reproduction in the male primate. We propose to use in situ hybridization for GnRH mRNA to study the physiological control of GnRH gene expression within individual neurons in the brain of the male macaque, Macaca fascicularis. We have plotted 4 major areas of investigation. The first concerns steroid hormone feedback. Testosterone serves a major role in the feedback control of GnRH secretion in the male primate, but the cellular mechanisms mediating this process remain obscure. In this aspect of the proposal, we will focus on determining whether gonadal hormones, and testosterone in particular, influence the level of GnRH mRNA in the brain; in addition, we will attempt to ascertain whether endogenous opioid pathways are involved in this negative feedback system. The second part concerns development. In primate species, the maturation of the reproductive system awaits only the augmentation of GnRH secretion, but the cellular mechanisms underlying the pubertal awakening of GnRH secretion are still unresolved. In this aspect of the proposal, we will focus on determining whether increases in GnRH mRNA can be implicated in controlling the onset of puberty in the primate. The third part concerns the problem of metabolic stress. Nutritional and metabolic status can have a profound influence on the secretion of GnRH in primates, but again, the cellular mechanisms mediating these disturbances remain unknown. We will attempt to ascertain whether changes in GnRH mRNA are responsible for changes in GnRH secretion caused by alterations in metabolism and to elucidate the possible role of glucocorticoids and corticotropin-releasing hormone in this process. Fourth, we will try to improve the methodology for conducting in situ hybridization analysis of GnRH mRNA in the brain. We believe this work will foster a better understanding of basic cellular neurobiology and help us to understand more about clinical problems related to human reproduction.
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