The overall goal of this proposed project is to define how the CREB transcription factor relays hormonal and environmental signals in the mammalian testis to genes within Sertoli and germ cells during spermatogenesis. The specific hypothesis to be tested is that alterations in the relative concentrations of activator and repressor CREB isoforms in the seminiferous tubules regulate the expression of cAMP-inducible genes required for the expansion and differentiation of male germ cells. One objective is to define the mechanisms responsible for the stage-specific expression of various CREB isoforms during the maturation of germ cells. A second objective of this study is to identify """"""""target"""""""" genes expressed in Sertoli and germ cells that are regulated by the cAMP signaling pathway and the CREB transcription factor.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HD034913-05
Application #
6343195
Study Section
Endocrinology Study Section (END)
Program Officer
Taymans, Susan
Project Start
1997-01-01
Project End
2001-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
5
Fiscal Year
2001
Total Cost
$78,861
Indirect Cost
Name
University of Pittsburgh
Department
Physiology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Scobey, M Joseph; Fix, Charity A; Walker, William H (2004) The Id2 transcriptional repressor is induced by follicle-stimulating hormone and cAMP. J Biol Chem 279:16064-70
Delfino, Frank J; Boustead, Jared N; Fix, Charity et al. (2003) NF-kappaB and TNF-alpha stimulate androgen receptor expression in Sertoli cells. Mol Cell Endocrinol 201:1-12
Shell, Scott A; Fix, Charity; Olejniczak, Donna et al. (2002) Regulation of cyclic adenosine 3',5'-monophosphate response element binding protein (CREB) expression by Sp1 in the mammalian testis. Biol Reprod 66:659-66
Scobey, M; Bertera, S; Somers, J et al. (2001) Delivery of a cyclic adenosine 3',5'-monophosphate response element-binding protein (creb) mutant to seminiferous tubules results in impaired spermatogenesis. Endocrinology 142:948-54
Delfino, F; Walker, W H (1999) Hormonal regulation of the NF-kappaB signaling pathway. Mol Cell Endocrinol 157:1-9
Delfino, F J; Walker, W H (1999) NF-kappaB induces cAMP-response element-binding protein gene transcription in sertoli cells. J Biol Chem 274:35607-13
Delfino, F; Walker, W H (1998) Stage-specific nuclear expression of NF-kappaB in mammalian testis. Mol Endocrinol 12:1696-707