The goal of this research proposal is to develop a greater understanding of the physiological mechanisms that control the onset of puberty in the primate. Using the male monkey, Macaca fascicularis, as a model for studying this problem, we will focus our efforts toward resolving how the body's metabolic control systems interact with its reproductive elements. This relationship is important, because we know that factors such as body weight and composition, metabolic rate, and nutritional status are intimately linked with pubertal maturation in human beings. First, we will examine the thesis that substrate-limited pathways of brain metabolism act to control luteinizing hormone-releasing hormone (LHRH) and gonadotropin secretion. We propose that changes in an animal's metabolic status, occurring as a function of life stage, is reflected in alterations in circulating metabolic hormones and substrates, which, in turn, serve as either signals or essential precursors for the synthesis of neurotransmitters engaged in regulating the LHRH pulse generator.
Our specific aim will be to identify these humoral factors and to elucidate their mechanisms of action. We suggest that this interaction between the metabolic and reproductive control systems and the resulting permissive influence on LHRH and gonadotropin secretion may be determinative in initiating the onset of puberty in primates and may also help to explain the etiology of reproductive failure associated with metabolic disorders and undernutrition in human beings. Second, using immunocytochemical and monoamine histofluorescence techniques, we propose to map the distribution and concentration of LHRH and catecholamine pathways in the medial basal hypothalamus of the developing monkey.
Our specific aim i s to identify changes in the neuroanatomical substrate, which may occur as a function of pubertal brain maturation. Together, these studies may help to foster a better understanding of human reproduction and could offer more insight into the clinical management of infertility.
Showing the most recent 10 out of 40 publications
