Interstitial tissue of mammalian testes consists of a variety of cell types including Leydig cells, macrophages, fibroblasts and components of the blood and lymphatic system. In rats, testicular macrophages represent about 20% of the interstitial tissue profile in histologic sections. Functions of testicular macrophages remain unknown. Testicular macrophages are often observed in intimate association with Leydig cells, and portions of Leydig cell cytoplasm are endocytosed by macrophages. Testicular macrophages in hypophysectomized rats bind 125I-FSH and increase their production of lactate in response to FSB. Recently, we reported that interleukin-l (IL-l) is a potent inhibitor of Leydig cell steroidogenesis in primary culture. Decreased testosterone formation may contribute to catabolic effects of the acute phase response to microbial invasion. Impaired reproductive functions that occur during infection may be in part mediated by increased IL-l production.
The aim of the present project is to further investigate the effects of IL-l on Leydig cell function and the interactions between macrophages and Leydig cells by: 1. Evaluating the in vivo and in vitro effects of IL-l on Leydig cell steroidogenesis. 2. Identifying IL-l receptors of Leydig cells 3. Identifying testicular IL-l by using Northern blot hybridization, in situ hybridization and immunocytochemical methods. 4. Isolating testicular macrophages. Macrophages will be stimulated with a variety of factors, such as FSH, lipopolysaccharide. and then co-cultured with Leydig cells. The effect of testicular macrophages on Leydig cell function will be evaluated.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD025641-01
Application #
3326843
Study Section
Reproductive Biology Study Section (REB)
Project Start
1989-05-01
Project End
1992-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Type
Schools of Medicine
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208
Lin, T; Wang, D; Nagpal, M L et al. (1994) Human chorionic gonadotropin decreases insulin-like growth factor-I gene transcription in rat Leydig cells. Endocrinology 134:2142-9
Nagpal, M L; Wang, D; Calkins, J H et al. (1994) Transformation and immortalization of Leydig cells from the Sprague-Dawley rat by an early genetic region of simian virus 40 DNA. Cell Tissue Res 275:459-65
Wang, D; Nagpal, M L; Lin, T et al. (1994) Insulin-like growth factor-binding protein-2: the effect of human chorionic gonadotropin on its gene regulation and protein secretion and its biological effects in rat Leydig cells. Mol Endocrinol 8:69-76
Lin, T; Wang, D; Nagpal, M L et al. (1994) Recombinant murine tumor necrosis factor-alpha inhibits cholesterol side-chain cleavage cytochrome P450 and insulin-like growth factor-I gene expression in rat Leydig cells. Mol Cell Endocrinol 101:111-9
Lin, T; Wang, D; Nagpal, M L (1993) Human chorionic gonadotropin induces interleukin-1 gene expression in rat Leydig cells in vivo. Mol Cell Endocrinol 95:139-45
Lin, T; Wang, D; Nagpal, M L et al. (1993) Expression and regulation of insulin-like growth factor-binding protein-1, -2, -3, and -4 messenger ribonucleic acids in purified rat Leydig cells and their biological effects. Endocrinology 132:1898-904
Lin, T; Wang, D; Nagpal, M L et al. (1992) Down-regulation of Leydig cell insulin-like growth factor-I gene expression by interleukin-1. Endocrinology 130:1217-24
Lin, T; Wang, T L; Nagpal, M L et al. (1991) Interleukin-1 inhibits cholesterol side-chain cleavage cytochrome P450 expression in primary cultures of Leydig cells. Endocrinology 129:1305-11
Nagpal, M L; Wang, D; Calkins, J H et al. (1991) Human chorionic gonadotropin up-regulates insulin-like growth factor-I receptor gene expression of Leydig cells. Endocrinology 129:2820-6
Wang, D L; Nagpal, M L; Calkins, J H et al. (1991) Interleukin-1 beta induces interleukin-1 alpha messenger ribonucleic acid expression in primary cultures of Leydig cells. Endocrinology 129:2862-6

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