Gonadotropin-releasing hormone (GnRH) and the subsequent release of luteinizing hormone (LH) is the final common pathway for the neuroendocrine control of reproduction. The factors regulating GnRH release are poorly understood. The recent discovery of the co-expression of the peptide orphanin FQ/nociceptin (OFQ/N) with almost all GnRH neurons in both sexes and in turn the ability of OFQ/N to reduce GnRH release in vitro suggests OFQ/N plays a part in the control of GnRH neuronal activity. The experiments herein will establish: a) if, as in hypothalamic blocks, OFQ/N can inhibit GnRH/LH release in vivo; b) if OFQ/N acts through its receptor, opioid receptor like-1 receptor (ORL-1), to directly effect GnRH neurons and/or gonadotropes; and c) if OFQ/N directly regulates GnRH/LH expression levels through ORL-1. Overall these studies will provide important information about the mechanisms regulating GnRH neuronal activity and the corresponding release of LH.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS049892-02
Application #
7100103
Study Section
Special Emphasis Panel (ZRG1-F02A (20))
Program Officer
Mitler, Merrill
Project Start
2005-08-01
Project End
2007-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
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Dooley, G P; Reardon, K F; Prenni, J E et al. (2008) Proteomic analysis of diaminochlorotriazine adducts in wistar rat pituitary glands and LbetaT2 rat pituitary cells. Chem Res Toxicol 21:844-51
Foradori, Chad D; Amstalden, Marcel; Coolen, Lique M et al. (2007) Orphanin FQ: evidence for a role in the control of the reproductive neuroendocrine system. Endocrinology 148:4993-5001
Foradori, Chad D; Lund, Trent D; Nagahara, Alan H et al. (2007) Corticotropin-releasing hormone heterogeneous nuclear RNA (hnRNA) and immunoreactivity are induced in extrahypothalamic brain sites by kainic-acid-induced seizures and are modulated by estrogen. Brain Res 1164:44-54