Abstract

This application addresses a number of questions regarding the activity both endogenous (Ghrelin) and synthetic (GH releasing peptide, GHRPs, such as MK-0677) ligands for the Growth Hormone Secretagogue Receptor (GHS-R) and the nature of their interaction. The application has an overall aim of elucidating the physiologic role of GHS-R, especially as it relates to aging. It is predicated on a significant amount of preliminary data, and driven by a number of hypotheses. Specifically, four aims are proposed: 1) determine the function of the octanoyl moiety on Ghrelin and its role in Ghrelin's interaction with the GHS-R, 2) using site directed mutagenesis, determine the characteristics of the GHS-R binding pocket(s) that interact with Ghrelin, a putative truncated Ghrelin 1-14, and synthetic GHRPs, 3) Determine whether Ghrelin and its potential alternate forms stimulate activity in hypothalamic neuron and define the hypothalamic neurons that respond to these ligands and, 4) determine whether aging is associated with a decline in Ghrelin activity; then whether such a putative decline is due to a decrease in Ghrelin acylating activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG018895-03
Application #
6631566
Study Section
Endocrinology Study Section (END)
Program Officer
Bellino, Francis
Project Start
2001-03-01
Project End
2005-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
3
Fiscal Year
2003
Total Cost
$336,375
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Other Health Professions
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Szentirmai, Eva; Kapás, Levente; Sun, Yuxiang et al. (2009) The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice. Proc Natl Acad Sci U S A 106:14069-74
Yang, Hyunwon; Dixit, Vishwa D; Patel, Kalpesh et al. (2008) Reduction in hypophyseal growth hormone and prolactin expression due to deficiency in ghrelin receptor signaling is associated with Pit-1 suppression: relevance to the immune system. Brain Behav Immun 22:1138-45
Sun, Yuxiang; Butte, Nancy F; Garcia, Jose M et al. (2008) Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance. Endocrinology 149:843-50
Sun, Yuxiang; Garcia, Jose Manuel; Smith, Roy G (2007) Ghrelin and growth hormone secretagogue receptor expression in mice during aging. Endocrinology 148:1323-9
Dixit, Vishwa Deep; Yang, Hyunwon; Sun, Yuxiang et al. (2007) Ghrelin promotes thymopoiesis during aging. J Clin Invest 117:2778-90
Szentirmai, Eva; Kapas, Levente; Sun, Yuxiang et al. (2007) Spontaneous sleep and homeostatic sleep regulation in ghrelin knockout mice. Am J Physiol Regul Integr Comp Physiol 293:R510-7
Wang, Guo-Li; Shi, Xiurong; Salisbury, Elizabeth et al. (2007) Growth hormone corrects proliferation and transcription of phosphoenolpyruvate carboxykinase in livers of old mice via elimination of CCAAT/enhancer-binding protein alpha-Brm complex. J Biol Chem 282:1468-78
Jiang, Hong; Betancourt, Lorena; Smith, Roy G (2006) Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Mol Endocrinol 20:1772-85
Sun, Yuxiang; Asnicar, Mark; Saha, Pradip K et al. (2006) Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice. Cell Metab 3:379-86
Smith, Roy G; Jiang, Hong; Sun, Yuxiang (2005) Developments in ghrelin biology and potential clinical relevance. Trends Endocrinol Metab 16:436-42

Showing the most recent 10 out of 14 publications