Abstract

This application proposes that basement membrane components of the seminiferous tubules play a determining role in Sertoli cell function and in the formation of a tubular lumen by a selective process of programmed cell death. To examine these possibilities, three approaches will be taken.
In Specific Aim 1, an in vitro seminiferous cord model using basement membrane components as a culture substrate will be used.
In Specific Aim 2, studies will be focused on the mechanism of signal transduction that occurs after basement membrane components bind to integrins on the surface of Sertoli cells. A major emphasis will be the role of Ca 2+ as a second messenger and protooncogene c-fos as a potential third messenger in Sertoli cell responses to the basement membrane.
In Specific Aim 3, the role of the basement membrane as a survival factor for Sertoli cells will be studied, in particular the role and mechanism of seminiferous tubular lumen formation related to Sertoli cell differentiation and its possible programmed cell death.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD016260-15
Application #
2673463
Study Section
Reproductive Biology Study Section (REB)
Project Start
1981-09-01
Project End
2001-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
15
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Georgetown University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057

  Publications

Richardson, L L; Kleinman, H K; Dym, M (1998) Altered basement membrane synthesis in the testis after tissue injury. J Androl 19:145-55
Jia, M C; Ravindranath, N; Papadopoulos, V et al. (1996) Regulation of c-fos mRNA expression in Sertoli cells by cyclic AMP, calcium, and protein kinase C mediated pathways. Mol Cell Biochem 156:43-9
Ravindranath, N; Papadopoulos, V; Brooker, G et al. (1996) Rat Sertoli cell calcium response to basement membrane and follicle-stimulating hormone. Biol Reprod 54:130-7
Okanlawon, A; Dym, M (1996) Effect of chloroquine on the formation of tight junctions in cultured immature rat Sertoli cells. J Androl 17:249-55
Dirami, G; Ravindranath, N; Kleinman, H K et al. (1995) Evidence that basement membrane prevents apoptosis of Sertoli cells in vitro in the absence of known regulators of Sertoli cell function. Endocrinology 136:4439-47
Dirami, G; Papadopoulos, V; Kleinman, H K et al. (1995) Identification of transferrin and inhibin-like proteins in matrigel. In Vitro Cell Dev Biol Anim 31:404-11
Richardson, L L; Kleinman, H K; Dym, M (1995) The effects of aging on basement membrane in the testis. J Androl 16:118-26
Richardson, L L; Kleinman, H K; Dym, M (1995) Basement membrane gene expression by Sertoli and peritubular myoid cells in vitro in the rat. Biol Reprod 52:320-30
Richardson, L L; Dym, M (1994) Improved adhesiveness of polyester wax sections for immunocytochemistry. Biotechniques 17:846-8
Dym, M (1994) Basement membrane regulation of Sertoli cells. Endocr Rev 15:102-15

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