Hypothalamic RFamide related peptide-3 (RFRP-3) neurons project to oxytocin and vasopressin neurons and stimulate secretion

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 142-166-Hypothalamus-Pituitary Development & Biology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-159
Maryam Karami Kheirabad1, Greg M Anderson2 and Mohammed Z Rizwan*3
1University of Otago, Dunedin, New Zealand, 2Univ of Otago Schl of Med Sci, Dunedin, New Zealand, 3University of Otago School of Medical Sciences, Dunedin, New Zealand
RFRP-3 is a hypothalamic RFamide neuropeptide that is best known for inhibition of gonadotropin-releasing hormone neuronal activity. RFRP-3 neurons are scattered within and just below the dorsomedial hypothalamus of rats, and project to a wide variety of brain regions including the paraventricular nucleus (PVN) (Rizwan et al 2009, Endocrinology 150: 1413-20) where their receptor (GPR147) mRNA is abundant (Rizwan et al 2012, Endocrinology 153: 3770-9). Furthermore, RFRP-3 neurons appear to contact corticotropin-releasing hormone neurons (which drive the stress axis) in this region in rats, and acute RFRP-3 treatment increased measures of anxiety-related behavior and restraint stress-induced corticosterone secretion. Co-treatment with the RFRP-3 receptor antagonist RF9 blocked these effects (Rizwan et al, unpublished observations). Oxytocin and vasopressin neurons, also synthesized in magnocellular and parvocellular neurons of the PVN are believed to play opposing roles to each other in behavioral and psychological tests for anxiety. In the current study we tested whether RFRP-3 neurons innervate and have biological effects on oxytocin and vasopressin neurons. We first measured whether RFRP-3 neurons project to oxytocin and vasopressin neurons in the PVN. Dual label immunohistochemistry combined with confocal microscopy revealed that in male, virgin female and lactating females (n=5 per group), 8-15% of oxytocin neurons and 21-35% of vasopressin neurons were apposed by RFRP-3 fibers, with no significant effects of sex or lactation. We next measured the effects of acute intracerebroventricular RFRP-3 administration (5 nmol) or blockade with RF9 (20 nmol) (n=5 per group) on oxytocin concentration in the blood after 20 minutes using enzyme immunoassay. RFRP-3 treatment increased oxytocin concentration fourfold in the blood of diestrus female rats compared to vehicle-treated controls (P<0.05), and co-treatment with RF9 blocked these effects. Measurement of vasopressin is currently in progress. Collectively, these findings reveal that RFRP-3 can act on oxytocin and possibly vasopressin neurons. It’s interaction with these neurons may assist in modulating anxiety and fear responses.

Nothing to Disclose: MKK, GMA, MZR

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Supported by the Royal Society of New Zealand Marsden Fund and the Lottery Health Research Grants Board.