title: Orphanin FQ inhibits GnRH secretion from rat hypothalamic fragments but not GT1-7 neurons.
abstract: Orphanin FQ is a novel opioid family member, which is densely localized in the hypothalamus, a region of the brain important for the control of reproduction. This study tested the hypothesis that orphanin FQ might regulate the secretion of gonadotropin-releasing hormone, the key central regulator of the ovulatory cycle. To test this hypothesis, we used rat hypothalamic fragments and immortalized gonadotropin-releasing hormone neurons (GT1-7) in vitro and examined whether orphanin FQ would inhibit forskolin-induced gonadotropin-releasing hormone release. The studies revealed that orphanin FQ potently and dose-dependently inhibits forskolin-induced gonadotropin-releasing hormone release from rat hypothalamic fragments. In contrast, orphanin FQ had no effect on gonadotropin-releasing hormone release from GT1-7 neurons. Reverse transcriptase-polymerase chain reaction analysis further revealed that the orphanin FQ receptor, ORL-1 is expressed in hypothalamic fragments, but not in GT1-7 neurons. Together, these findings are the first to suggest a role for orphanin FQ in the regulation of gonadotropin releasing hormone secretion.
authors.affiliation: Institute of Molecular Medicine and Genetics, Neurobiology Program, and Department of Neurology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912, USA.
authors.forename: Krishnan M
authors.initials: KM
authors.lastname: Dhandapani
authors.forename: Darrell W
authors.initials: DW
authors.lastname: Brann
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D005576:Colforsin; D007987:Gonadotropin-Releasing Hormone; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat