Physical and psychological stress are known to activate the hypothalamic-pituitary-adrenal (HPA) axis; however, stress has also been shown to negatively impact the HP-gonadal (HPG) axis. Studies have demonstrated that Corticotropin-Releasing Hormone (CRH), the key hypophysiotrophic effector molecule of the HPA axis, plays a significant role in stress-induced inhibition of reproduction. While CRH is known to act centrally, regulation may exist at the pituitary. CRH binds two receptors and a CRH binding protein (CRHBP), a 37kD glycoprotein thought to be an important modulator of CRH activity. Both CRH-receptors and CRHBP have recently been localized to murine gonadotrope, the primary pituitary cell type involved in reproductive signaling. This localization and the dramatic GnRH-induced increases in CRHBP expression in gonadotrope-like cells suggest that the gonadotrope should be reexamined as a potential site for HPA/HPG interactions and that CRHBP may play an important role in modulating these interactions. This proposal will examine GnRH regulation of endogenous CRHBP expression, molecular mechanisms mediating GnRH induced CRHBP gene regulation, and CRHBP modulation of CRH/HPG interactions in gonadotrope. An understanding of how reproductive hormones regulate CRHBP expression and how CRHBP modulates CRH activity will be important for our understanding of diseases involving CRH dysregulation, including deoression anorexia, anxiety and reproductive disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS048775-01A1
Application #
6884256
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Mitler, Merrill
Project Start
2005-03-01
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
1
Fiscal Year
2004
Total Cost
$34,156
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biochemistry
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109