Abstract

The long-term objective of this project is to characterize the mechanisms by which human choriogonadotropin (hCG) and other hormones regulate steroid biosynthesis in cultured Leydig tumor cells.
The specific aims are as follows: (1) identification of heterologous hormones that regulate hCG receptors; (2) characterization of the effects of receptor regulation on hCG actions; (3) elucidation of the mechanisms by which heterologous hormones regulate hCG receptors; (4) characterization of the role of adenylate cyclase and protein kinases in the hormonal control of steroid biosynthesis; and (5) characterization of the mobilization of cholesterol used for steroid biosynthesis. Studies on these phenomena will be carried out using a combination of biochemical and genetic approaches and are expected to provide information about the regulation of polypeptide hormone receptors, gonadotropin action, and regulation of steroid biosynthesis. (C)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040629-03
Application #
3180897
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1985-02-01
Project End
1988-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Population Council
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10017

  Publications

Matzkin, Maria Eugenia; Yamashita, Soichi; Ascoli, Mario (2013) The ERK1/2 pathway regulates testosterone synthesis by coordinately regulating the expression of steroidogenic genes in Leydig cells. Mol Cell Endocrinol 370:130-7
Tai, Ping; Ascoli, Mario (2011) Reactive oxygen species (ROS) play a critical role in the cAMP-induced activation of Ras and the phosphorylation of ERK1/2 in Leydig cells. Mol Endocrinol 25:885-93
Yamashita, Soichi; Tai, Ping; Charron, Jean et al. (2011) The Leydig cell MEK/ERK pathway is critical for maintaining a functional population of adult Leydig cells and for fertility. Mol Endocrinol 25:1211-22
Tai, Ping; Shiraishi, Koji; Ascoli, Mario (2009) Activation of the lutropin/choriogonadotropin receptor inhibits apoptosis of immature Leydig cells in primary culture. Endocrinology 150:3766-73
Galet, Colette; Ascoli, Mario (2008) Arrestin-3 is essential for the activation of Fyn by the luteinizing hormone receptor (LHR) in MA-10 cells. Cell Signal 20:1822-9
Shiraishi, Koji; Ascoli, Mario (2008) A co-culture system reveals the involvement of intercellular pathways as mediators of the lutropin receptor (LHR)-stimulated ERK1/2 phosphorylation in Leydig cells. Exp Cell Res 314:25-37
Shiraishi, Koji; Ascoli, Mario (2007) Lutropin/choriogonadotropin stimulate the proliferation of primary cultures of rat Leydig cells through a pathway that involves activation of the extracellularly regulated kinase 1/2 cascade. Endocrinology 148:3214-25
Ascoli, Mario (2007) Potential Leydig cell mitogenic signals generated by the wild-type and constitutively active mutants of the lutropin/choriogonadotropin receptor (LHR). Mol Cell Endocrinol 260-262:244-8
Galet, Colette; Ascoli, Mario (2006) A constitutively active mutant of the human lutropin receptor (hLHR-L457R) escapes lysosomal targeting and degradation. Mol Endocrinol 20:2931-45
Shiraishi, Koji; Ascoli, Mario (2006) Activation of the lutropin/choriogonadotropin receptor in MA-10 cells stimulates tyrosine kinase cascades that activate ras and the extracellular signal regulated kinases (ERK1/2). Endocrinology 147:3419-27

Showing the most recent 10 out of 47 publications