ROLE OF PACAP IN THE MALE FETAL PITUITARY

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DESCRIPTION (provided by applicant): Sexual maturation in the male is a complex process that involves changes in the hypothalamus, pituitary, testes, and secondary sexual organs and in their interrelationships. Improper development of any one of these components can lead to infertility in adult life. Infertility affects approximately 15% of couples, 40% of which are male factor infertility. Therefore, a complete understanding of the events associated with male sexual development may allow for early detection and possible prevention of infertility during adulthood. Furthermore, elucidation of the numerous factors that regulate male reproductive function could enhance the development of male contraceptive strategies. Our laboratory has been investigating the involvement of pituitary adenylate cyclase activating polypeptide (PACAP) in the regulation of the gonadotropin axis. We have previously demonstrated that PACAP is able to differentially regulate the two pituitary gonadotropins in vitro. PACAP has been shown to stimulate alpha subunit expression, stabilize LH-beta mRNA, and suppress FSH-beta mRNA expression. Our preliminary data in fetal male rats demonstrate a significant decline in pituitary PACAP at birth that is reciprocal to a dramatic rise in FSH-beta expression. We hypothesize that PACAP plays an important role in the development and maturation of the pituitary gonadotropin system. Specifically, we propose to 1) Provide anatomical, molecular and developmental evidence for dynamic changes in pituitary PACAP and its receptors during fetal and neonatal development. 2) Provide evidence that pituitary derived PACAP differentially regulates the gonadotropins during embryonic development. 3) Use gonadotroph and folliculostellate cell lines to demonstrate that pituitary products and endocrine hormones confer the high level of PACAP gene expression within the fetal anterior pituitary gland 4) Confirm the importance of PACAP on gonadotroph development by analyses of the affects of PACAP deficiency in PACAP-KO mice.