Abstract

Paracrine interactions play an important role in cellular communication within the testis. The presence of opioid peptides and their receptors in the testis has suggested that this peptide family may function, at least in part, as local regulators of testicular function. The PI has succeeded in identifying multiple testicular cell types that express the gene for the opioid peptide precursor, proenkephalin: spermatogenic cells and Sertoli cells. Proenkephalin-derived peptides therefore may mediate intratesticular actions of somatic as well as male germ cells that are important for the regulation of spermatogenesis. In addition, rat and mouse spermatogenic cells contain a unique 1700-nucleotide form of proenkephalin RNA, not found in somatic cells, that is developmentally regulated. The proenkephalin gene thus serves as a model for the regulation of germ-cell gene expression.
The aims of this proposal are: (1) to characterize the cis-acting elements within the proenkephalin gene responsible for its expression and developmental stage-specific regulation in spermatogenic cells: and (2) to characterize the translation products derived from proenkephalin RNA in the different testicular cells in which it is present. The latter experiments will be important for the ultimate elucidation of the functions of testicular proenkephalin-derived peptides.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036468-05
Application #
3234892
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1986-02-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Worcester Foundation for Biomedical Research
Department
Type
DUNS #
City
Shrewsbury
State
MA
Country
United States
Zip Code
01545

  Publications

Wang, Hang; San Agustin, Jovenal T; Witman, George B et al. (2004) Novel role for a sterol response element binding protein in directing spermatogenic cell-specific gene expression. Mol Cell Biol 24:10681-8
Wang, Hang; Liu, Feng; Millette, Clarke F et al. (2002) Expression of a novel, sterol-insensitive form of sterol regulatory element binding protein 2 (SREBP2) in male germ cells suggests important cell- and stage-specific functions for SREBP targets during spermatogenesis. Mol Cell Biol 22:8478-90
Persengiev, S P; Li, J; Poulin, M L et al. (2001) E2F2 converts reversibly differentiated PC12 cells to an irreversible, neurotrophin-dependent state. Oncogene 20:5124-31
Liu, F; Kondova, I; Kilpatrick, D L (2000) Detection of PACH1, a nuclear factor implicated in the transcriptional regulation of meiotic and early haploid stages of spermatogenesis. Mol Reprod Dev 57:224-31
Persengiev, S P; Kondova, I I; Kilpatrick, D L (1999) E2F4 actively promotes the initiation and maintenance of nerve growth factor-induced cell differentiation. Mol Cell Biol 19:6048-56
Chang, B B; Persengiev, S P; de Diego, J G et al. (1998) Proximal promoter sequences mediate cell-specific and elevated expression of the favorable prognosis marker TrkA in human neuroblastoma cells. J Biol Chem 273:39-44
Liu, F; Tokeson, J; Persengiev, S P et al. (1997) Novel repeat elements direct rat proenkephalin transcription during spermatogenesis. J Biol Chem 272:5056-62
Persengiev, S P; Kondova, I I; Millette, C F et al. (1997) Gli family members are differentially expressed during the mitotic phase of spermatogenesis. Oncogene 14:2259-64
Persengiev, S P; Robert, S; Kilpatrick, D L (1996) Transcription of the TATA binding protein gene is highly up-regulated during spermatogenesis. Mol Endocrinol 10:742-7
Poluha, W; Poluha, D K; Chang, B et al. (1996) The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. Mol Cell Biol 16:1335-41

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