Previous studies on testicular Leydig cell function have been performed in vivo or in dispersed cell suspension and have concentrated primarily on the role of gonadotropin in Leydig cell function. In the present study we propose to use a serum-free hormone supplemented culture system to study the effects of a variety of hormones, transport proteins, and growth factors on several parameters of Leydig cell function under defined conditions. A non-tumorigenic mouse clonal cell line, TM3, will be used as the most precisely defined cell culture system. In addition, primary cultures of Leydig cells will be studied from the rat, mouse and pig in order to have a cross-species comparison of the response of an established cell line and primary cultures from the same species. Parameters to be measured include cell survival and growth, steroid secretion (basal and hCG-stimulated), prostaglandin secretion, hormone receptor levels (androgen, progestin, insulin, EGF, hCG) and secreted protein. A set of hormone-supplements will be defined which are optimal for each function. These are expected to be overlapping but not identical. These studies should advance our understanding of the complex interrelationships of the hormonal control of Leydig cell function.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD016149-06
Application #
3313488
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1982-09-30
Project End
1991-03-31
Budget Start
1989-07-01
Budget End
1991-03-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Population Council
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10017
Kanzaki, M; Morris, P L (1999) Growth hormone regulates steroidogenic acute regulatory protein expression and steroidogenesis in Leydig cell progenitors. Endocrinology 140:1681-6
Kanzaki, M; Morris, P L (1998) Lactogenic hormone-inducible phosphorylation and gamma-activated site-binding activities of Stat5b in primary rat Leydig cells and MA-10 mouse Leydig tumor cells. Endocrinology 139:1872-82
Jenab, S; Morris, P L (1998) Testicular leukemia inhibitory factor (LIF) and LIF receptor mediate phosphorylation of signal transducers and activators of transcription (STAT)-3 and STAT-1 and induce c-fos transcription and activator protein-1 activation in rat Sertoli but not germ ce Endocrinology 139:1883-90
Kanzaki, M; Morris, P L (1998) Identification and regulation of testicular interferon-gamma (IFNgamma) receptor subunits: IFNgamma enhances interferon regulatory factor-1 and interleukin-1beta converting enzyme expression. Endocrinology 139:2636-44
Jenab, S; Morris, P L (1997) Transcriptional regulation of Sertoli cell immediate early genes by interleukin-6 and interferon-gamma is mediated through phosphorylation of STAT-3 and STAT-1 proteins. Endocrinology 138:2740-6
Jenab, S; Morris, P L (1996) Differential activation of signal transducer and activator of transcription (STAT)-3 and STAT-1 transcription factors and c-fos messenger ribonucleic acid by interleukin-6 and interferon-gamma in Sertoli cells. Endocrinology 137:4738-43
Boffa, L C; Morris, P L; Carpaneto, E M et al. (1996) Invasion of the CAG triplet repeats by a complementary peptide nucleic acid inhibits transcription of the androgen receptor and TATA-binding protein genes and correlates with refolding of an active nucleosome containing a unique AR gene sequence. J Biol Chem 271:13228-33
Okuda, Y; Bardin, C W; Hodgskin, L R et al. (1995) Interleukins-1 alpha and -1 beta regulate interleukin-6 expression in Leydig and Sertoli cells. Recent Prog Horm Res 50:367-72
Morris, P L; Hodgskin, L R; Fujisawa, M (1994) A spermatid factor inhibits cAMP and calcium signaling in Sertoli but not Leydig cells. Recent Prog Horm Res 49:353-8
Fantoni, G; Morris, P L; Forti, G et al. (1993) Endothelin-1: a new autocrine/paracrine factor in rat testis. Am J Physiol 265:E267-74

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