title: Central and peripheral effects of RFamide-related peptide-3 on luteinizing hormone and prolactin secretion in rats.
abstract: Hypothalamic RFamide-related peptide-3 (RFRP-3) neurons inhibit LH secretion via a central action. A direct hypophysiotropic action on the gonadotropes has also been suggested. To assess central RFRP-3 effects on the GnRH/LH surge that induces ovulation, ovariectomized rats were subjected to an estradiol plus progesterone surge-induction protocol. Chronic infusion of RFRP-3 (2.5 or 25 ng/h, intracerebroventricularly) caused a dose-dependent 50-60% inhibition of GnRH neuronal activation (assessed by colocalization with the immediate early gene c-Fos) at the surge peak compared with vehicle-treated controls. RFRP-3 also suppressed neuronal activation in the anteroventral periventricular region, which provides stimulatory input to GnRH neurons, by 50-80% compared with control values. To test whether centrally administered RFRP-3 inhibits pulsatile GnRH/LH secretion, chronically ovariectomized, low-level estradiol-treated rats without surge induction were blood sampled every 10 min for 4 h. Bolus injection of RFRP-3 (0, 2.5, or 25 microg, intracerebroventricularly) after 1.5 h did not affect subsequent LH pulse frequency, pulse amplitude, or the mean concentrations of LH or prolactin. RFRP-3 treatment of isolated anterior pituitary cells at moderate doses of up to 10(-7) m did not significantly inhibit LH release, either with or without GnRH cotreatment. These data reveal a central inhibitory effect of RFRP-3 on the hypothalamo-pituitary gonadal axis specifically during the estradiol-induced GnRH/LH surge. This effect may include actions of RFRP-3 on GnRH neurons and/or their anteroventral periventricular afferent inputs but is unlikely to involve direct inhibition of LH secretion at the level of the gonadotrope.
authors.affiliation: Department of Anatomy and Structural Biology, Centre for Neuroendocrinology, University of Otago School of Medical Sciences, Dunedin, New Zealand. greg.anderson@anatomy.otago.ac.nz
authors.forename: Greg M
authors.initials: GM
authors.lastname: Anderson
authors.forename: Hana-Lee
authors.initials: HL
authors.lastname: Relf
authors.forename: Mohammed Z
authors.initials: MZ
authors.lastname: Rizwan
authors.forename: John J
authors.initials: JJ
authors.lastname: Evans
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007986:Luteinizing Hormone / Q000097:blood* / Q000378:metabolism; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010052:Ovariectomy; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; C416987:RFamide peptide; D007987:Gonadotropin-Releasing Hormone; D011388:Prolactin; D007986:Luteinizing Hormone