The long-term objectives of the proposed research are the development of a better understanding of cellular functions and interactions in the testis and the influence of the somatic cells on the maintenance and control of spermatogenesis. Specifically those interactions between seminiferous peritubular cells and Sertoli cells mediated via soluble peptides will be examined.
Four specific aims are proposed: 1) to sequence and develop a molecular cDNA probe for the paracrine factor produced by peritubular cells (P) which modulates (Mod) Sertoli cell (S) function, PModS; 2) to elucidate the mechanism of action of PModS and examine the effects of PMOdS on various Sertoli cell functions; 3) to elucidate the hormonal and developmental regulation of PModS production and immunoneutralize PModS and transforming growth factors alpha and beta in the seminiferous tubule. The peritubular cells and Sertoli cells utilized in the study will be isolated from rat testes. Results of the proposed research will provide information on peritubular cell-Sertoli cell interactions, the hormonal control of these interactions, and the influence of these cellular interactions on the maintenance and control of spermatogenesis. Information from the proposed studies is essential for the future design of male contraceptives and fertility agents. In addition, the research will provide insight into general mesenchymal-epithelial cell interactions which are important for the physiology of many different tissues.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020583-09
Application #
2198046
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1986-12-01
Project End
1995-11-30
Budget Start
1993-12-01
Budget End
1995-11-30
Support Year
9
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Levine, E; Cupp, A S; Miyashiro, L et al. (2000) Role of transforming growth factor-alpha and the epidermal growth factor receptor in embryonic rat testis development. Biol Reprod 62:477-90
Chaudhary, J; Cupp, A S; Skinner, M K (1997) Role of basic-helix-loop-helix transcription factors in Sertoli cell differentiation: identification of an E-box response element in the transferrin promoter. Endocrinology 138:667-75
Chaudhary, J; Whaley, P D; Cupp, A et al. (1996) Transcriptional regulation of sertoli cell differentiation by follicle-stimulating hormone at the level of the c-fos and transferrin promoters. Biol Reprod 54:692-9
Chaudhary, J; Skinner, M K (1995) Transcriptional regulation of Sertoli cell differentiation (transferrin promoter activation) during testicular development. Dev Genet 16:114-8
Whaley, P D; Chaudhary, J; Cupp, A et al. (1995) Role of specific response elements of the c-fos promoter and involvement of intermediate transcription factor(s) in the induction of Sertoli cell differentiation (transferrin promoter activation) by the testicular paracrine factor PModS. Endocrinology 136:3046-53
Mullaney, B P; Rosselli, M; Skinner, M K (1994) Developmental regulation of Sertoli cell lactate production by hormones and the testicular paracrine factor, PModS. Mol Cell Endocrinol 104:67-73
Norton, J N; Vigne, J L; Skinner, M K (1994) Regulation of Sertoli cell differentiation by the testicular paracrine factor PModS: analysis of common signal transduction pathways. Endocrinology 134:149-57
Mullaney, B P; Skinner, M K (1993) Transforming growth factor-beta (beta 1, beta 2, and beta 3) gene expression and action during pubertal development of the seminiferous tubule: potential role at the onset of spermatogenesis. Mol Endocrinol 7:67-76
Norton, J N; Skinner, M K (1992) Regulation of Sertoli cell differentiation by the testicular paracrine factor PModS: potential role of immediate-early genes. Mol Endocrinol 6:2018-26
Risbridger, G P; Skinner, M K (1992) Evaluation of the effect of peritubular cell secretions and the testicular paracrine factor P-Mod-S on Leydig cell steroidogenesis and immunoactive inhibin production. Int J Androl 15:73-83

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