Abstract

The long-term objective of this project is to discover how gonadotropins act. In this application, we propose to develop and use monoclonal antibodies which bind to LH-, FSH-, and hCG- receptor complexes to study the orientation of the hormones after they bind to testicular receptors. We will monitor changes in the orientation of the hormone to identify events such as receptor clustering and internalization. In addition, we will utilize the monoclonal antibody tools to quantify the amounts of LH and FSH which become bound to testicular receptors in vivo. These latter experiments are designed to study the coupling of receptor occupancy to response in physiological conditions. Specifically we want to investigate the mechanisms responsible for increased testosterone secretion seen in the absence of changes in levels of circulating LH.

  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 #
5R01HD014907-09
Application #
3312860
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1983-08-01
Project End
1993-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Medicine
DUNS #
622146454
City
Piscataway
State
NJ
Country
United States
Zip Code
08854

  Publications

Moyle, William R; Lin, Win; Myers, Rebecca V et al. (2005) Models of glycoprotein hormone receptor interaction. Endocrine 26:189-205
Bernard, Michael P; Lin, Win; Myers, Rebecca et al. (2005) Crosslinked bifunctional gonadotropin analogs with reduced efficacy. Mol Cell Endocrinol 233:25-31
Xing, Yongna; Myers, Rebecca V; Cao, Donghui et al. (2004) Glycoprotein hormone assembly in the endoplasmic reticulum: IV. Probable mechanism of subunit docking and completion of assembly. J Biol Chem 279:35458-68
Xing, Yongna; Myers, Rebecca V; Cao, Donghui et al. (2004) Glycoprotein hormone assembly in the endoplasmic reticulum: I. The glycosylated end of human alpha-subunit loop 2 is threaded through a beta-subunit hole. J Biol Chem 279:35426-36
Xing, Yongna; Myers, Rebecca V; Cao, Donghui et al. (2004) Glycoprotein hormone assembly in the endoplasmic reticulum: III. The seatbelt and its latch site determine the assembly pathway. J Biol Chem 279:35449-57
Xing, Yongna; Lin, Win; Jiang, Mei et al. (2004) Use of protein knobs to characterize the position of conserved alpha-subunit regions in lutropin receptor complexes. J Biol Chem 279:44427-37
Xing, Yongna; Myers, Rebecca V; Cao, Donghui et al. (2004) Glycoprotein hormone assembly in the endoplasmic reticulum: II. Multiple roles of a redox sensitive beta-subunit disulfide switch. J Biol Chem 279:35437-48
Bernard, Michael P; Cao, Donghui; Myers, Rebecca V et al. (2004) Tight attachment of chitin-binding-domain-tagged proteins to surfaces coated with acetylated chitosan. Anal Biochem 327:278-83
Moyle, William R; Xing, Yongna; Lin, Win et al. (2004) Model of glycoprotein hormone receptor ligand binding and signaling. J Biol Chem 279:44442-59
Bernard, Michael P; Lin, Win; Cao, Donghui et al. (2004) Only a portion of the small seatbelt loop in human choriogonadotropin appears capable of contacting the lutropin receptor. J Biol Chem 279:44438-41

Showing the most recent 10 out of 33 publications