Data suggest that the neonatal period is a second critical interval (in addition to the prenatal period) when the nervous system is sensitive to the organizational effects of androgens, and that early postnatal treatment with gonadotropin releasing hormone (GnRH) analogues alters early programming of immune responses in male primates. This proposal seeks to expand the understanding of the importance of neonatal testosterone in sexual and behavioral development and to further assess the impact of neonatal treatment with GnRH analogues on the development of the immune system in male primates. Using animals treated as neonates with a GnRH antagonist, the investigators will further examine the importance of neonatal activation of the pituitary-testicular axis on the timing of puberty, peripubertal endocrine events, skeletal maturation, postpubertal reproductive function (including fertility), and peripubertal and postpubertal sexual and aggressive behavior and laterality. Efforts will continue to define the site(s) (hypothalamus, pituitary or testis) of the physiological defect responsible for abnormal sexual and behavioral function in animals treated as neonates with GnRH analogues. Animals will be tethered and used to assess whether GnRH pulsatility (as measured indirectly by LH assay) is altered by treatment. The tethered animals will also be used to assess the involvement of the endogenous opioid system, CRH and/or subnormal testosterone levels in mediating the reduced gonadotropin response of treated monkeys to excitatory amino acids. The effect of treatment on fertility, Leydig cell ultrastructure, testicular morphology, and spermatogenic efficiency will also be examined. The investigators will also assess the impact of neonatal treatment with a GnRH antagonist or antagonist and androgen on the development of immune function. They will perform experiments designed to identify the effects of neonatal GnRH analogue treatment on: 1) lymphocyte subsets distribution and immunoglobulin production; 2) development of specific immune responses to selected antigens; and 3) selection of the T cell receptor gene products repertoire. The proposed studies will further the understanding of mechanisms governing sexual, skeletal, behavioral and immune system development, and the role that neonatal testosterone plays in this process.
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