Abstract

In this application, it is postulated that the effects of gonadal steroids on immunity are mediated, at least in part, at the level of the thymus via thymocyte proliferation and programmed cell death. This proposal examines the role of androgenic hormones in thymic involution and the development of the immune repertoire. The four specific aims are to (1) define the cellular targets for androgen-induced thymocyte apoptosis; (2) define the cellular targets mediating androgen effects on tissue-specific proliferation; (3) interrupt intrathymic androgen signaling pathways and examine resulting immune system composition and function; and (4) define the role of TGF-b in the mediation of androgen-induced thymic involution.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK041053-08
Application #
2404269
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Linder, Barbara
Project Start
1989-02-01
Project End
2001-06-30
Budget Start
1997-09-30
Budget End
1998-06-30
Support Year
8
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212

  Publications

Olsen, Nancy J; Kovacs, William J (2002) Hormones, pregnancy, and rheumatoid arthritis. J Gend Specif Med 5:28-37
Olsen, N J; Gu, X; Kovacs, W J (2001) Bone marrow stromal cells mediate androgenic suppression of B lymphocyte development. J Clin Invest 108:1697-704
Olsen, N J; Olson, G; Viselli, S M et al. (2001) Androgen receptors in thymic epithelium modulate thymus size and thymocyte development. Endocrinology 142:1278-83
Olsen, N J; Viselli, S M; Fan, J et al. (1998) Androgens accelerate thymocyte apoptosis. Endocrinology 139:748-52
Viselli, S M; Reese, K R; Fan, J et al. (1997) Androgens alter B cell development in normal male mice. Cell Immunol 182:99-104
Olsen, N J; Kovacs, W J (1996) Gonadal steroids and immunity. Endocr Rev 17:369-84
Viselli, S M; Olsen, N J; Shults, K et al. (1995) Immunochemical and flow cytometric analysis of androgen receptor expression in thymocytes. Mol Cell Endocrinol 109:19-26
Viselli, S M; Stanziale, S; Shults, K et al. (1995) Castration alters peripheral immune function in normal male mice. Immunology 84:337-42
Olsen, N J; Viselli, S M; Shults, K et al. (1994) Induction of immature thymocyte proliferation after castration of normal male mice. Endocrinology 134:107-13
Olsen, N J; Zhou, P; Ong, H et al. (1993) Testosterone induces expression of transforming growth factor-beta 1 in the murine thymus. J Steroid Biochem Mol Biol 45:327-32

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