This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The sequence of events in sexual development is very important. An inappropriate hormonal environment can result in infertility of the adult male. Infertility affects approximately 15% of couples, 40% are male infertility. An understanding of hormonal regulation of male sexual development may allow for early detection and prevention of infertility. The goals of this plan are to develop an understanding of regulation of the differential expression of the pituitary gonadotropins during maturation. There is data suggesting that pituitary adenylate cyclase activating polypeptide (PACAP) can differentially regulate the pituitary gonadotropins. PACAP increases the actions of gonadotropin releasing hormone (GnRH) and alone PACAP enhances the production of luteinizing hormone while decreasing follicle stimulating hormone expression. Our overall hypothesis is that during embryonic and early postnatal development, the pituitary is exposed to very high levels of PACAP that selectively suppress FSH until the juvenile stage of sexual maturity.
The specific aims of this proposal are: 1) To determine whether PACAP plays a role in the differential expression of the gonadotropin subunit genes during fetal pituitary development; 2) To determine if the rise in FSHb mRNA in immature male rats is related to weaning, and is coincident with a change in PACAP expression; 3) To determine if pituitary cells from fetal and infant male rats are more responsive to PACAP than are cells from juvenile rats; and 4) To explore the developmental effects of PACAP through pituitary specific expression of the PACAP antagonist PACAP-(6-38). The proposed experiments will develop the PI s skills in the techniques of pituitary cell culture, in situ hybridization, laser capture microdissection, single cell RT-PCR, in situ hybridization, Northern hybridization, Southern hybridization, and cDNA cloning. Successful completion of this proposal should provide insight into developmental regulation of gonadotropins and invaluable experience that the candidate can utilize to propagate a successful career.
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