Analysis of the cellular and molecular mechanisms mediating peptide hormone action constitutes an important component of the research efforts of the Reproductive Neuroendocrinology Section. The close interrelationships mediating neuroendocrine responses within the hypothalamic-pituitary-gonadal system offer an excellent opportunity to analyze some unique characteristics of peptide-peptide, peptide-amine, and peptide-amine-steroid interactions. Studies using pituitary cell cultures are directed to evaluate the precise mechanisms through which peptidergic or aminergic secretagogues enhance or suppress peptide hormone release. A main target of our research efforts will be the role of input signal on modifying cellular responses, using a computerized perifusion system that can exquisitely regulate pulse delivery to cells or tissues (in vitro) of appropriately designed hormone signals. Other protocols are designed to evaluate characteristics of hormone-receptor interactions, post-receptor as well as transmembrane events involved in the hormone-releasing process, and definition of the specific intracellular messengers transducing the action of key hypothalamic peptides involved in pituitary hormone release. At the testicular level, studies are designed to determine the intratesticular effects of LHRH-analogs known to adversely affect both the endocrine and the gametogenic functions of the testis. Since some of these analogs are presently being tested for use in human contraception, an understanding of their site(s) and mechanisms of action is of obvious significance. The interaction of these LHRH-A with intrinsinc peptidergic systems within the testis, such as the proopiomelanocortin-derived peptides, is also being explored. The results may provide very significant advances to our knowledge of paracrine and/or autocrine effects of gonadal peptides.
