This proposal represent the first comprehensive effort to characterize and understand the mechanisms controlling the annual testicular cycle in a long-day breeding cervid species, the Eld's deer. The objectives are to relate seasonal changes in endocrine function with tests activity and to study the sensitivity of the hypogonadal, sexually inactive male to a constant exogenous infusion of a synthetic hypothalamic hormone (gonadotropin releasing hormone [GnRH] agonist). Studies are designed to determine the dynamics of pituitary and testicular responsiveness by intensive serial blood sampling combined with GnRH agonist challenges which will detect subtle differences in endogenous immunoreactive and bioactive hormone pulses. This information will be examined in the context of seasonal variations in steroidogenesis and nonendocrine tests activity including assessments of semen volume, sperm concentration, motility and structural integrity, histological estimates of spermatogenesis and luteinizing hormone receptor content as well as gross morphometry. A low dosage of GnRH agonist will be infused continuously into males in the nonbreeding season, thereby measuring the responsiveness of the pituitary and tests as well as our ability to control spermatogenesis. From a fundamental science perspective, new information will be generated on:1) the details of estrogen and androgen steroidogenesis and metabolism in relation to seasonal testis function;2) reproductive-endocrine dynamics associated with seasonal breeding;3) in vitro testicular responsiveness to exogenous LH and the potential direct inhibitory effects of estradiol-17 beta ;4) immunoreactive versus bioactive gonadotropin secretion for assessing pituitary sensitivity;5) the efficacy of stimulating testis function in hypogonadal males by continuous low-dose infusions of a GnRH agonist; and 6) the utility of cervid species as an alternative model for understanding the mechanisms regulating testicular activity. This proposal also affords unique training opportunity for the Candidate, allowing career development as a specialist in the reproductive physiology and endocrinology of male reproduction. A multidisciplinary approach will provide a comprehensive understanding of the complex fertility process. The Candidate will receive extensive training from 8 established investigators in fundamental research concepts and sophisticated biotechniques including immuno- and bio- assay of gonadotropic hormones, radioreceptor assays, in vitro tissue culture, steroid biochemistry and histological assessment of testicular tissues.
