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Title: Effects of RFRP2 and RF9 on secretion of luteinizing hormone in prepubertal gilts

item Thorson, Jennifer
item PREZOTTO, LIGIA - North Dakota State University
item MCCOSH, RICHARD - West Virginia University
item Wright, Elane
item SWANSON, KENDALL - North Dakota State University
item WHITE, BRETT - University Of Nebraska
item Freking, Bradley - Brad
item Oliver, William
item HILEMAN, STANLEY - West Virginia University
item Lents, Clay

Submitted to: Endocrine Society Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 3/27/2014
Publication Date: 6/1/2014
Citation: Thorson, J.F., Prezotto, L.D., McCosh, R.B., Wright, E.C., Swanson, K.C., White, B.R., Freking, B.A., Oliver, W.T., Hileman, S.M., Lents, C.A. 2014. Effects of RFRP2 and RF9 on secretion of luteinizing hormone in prepubertal gilts [abstract]. In: Endocrine Society’s 96th Annual Meeting and Expo (ICE/ENDO 2014), June 21-24, 2014, Chicago, IL. Endocrine Reviews. 35(3 Supplement):SUN-0669.

Interpretive Summary:

Technical Abstract: In most mammals, the RF-amide related peptide (RFRP) pre-pro-protein contains cleavage sites for 2 peptides (RFRP1 and RFRP3). Our laboratory did not observe RFRP3-induced suppression of LH secretion in gilts. However, the porcine sequence encodes an additional peptide (RFRP2) with an amidated C-terminus identical to avian gonadotropin-inhibitory hormone (GnIH). Moreover, a selective antagonist for the neuropeptide FF (NPFF) receptors (RF9) has been shown to potently induce a release of LH in mammals, thus providing an additional approach for studying the RFRP system in the pig. We hypothesized that RFRP2 reduces secretion of LH in the prepubertal gilt, while RF9 stimulates the release of LH. Prepubertal gilts were fitted with indwelling catheters to allow for intravenous treatment and collection of serial blood samples (10-minute intervals over 8 hours) for analysis of LH. In experiment 1, ovariectomized gilts (n = 9) were used in a replicated 3×3 Latin Square design with 6 days between treatment crossover. Treatments were saline and RFRP2 administered at 0.01 or 0.1 mg/kg BW. The RFRP2 was administered in a loading dose (25% of entire dose) followed by 11 repeated injections at 10-minute intervals. Two hours after treatment concluded, a GnRH antagonist (SB75; 10 µg/kg BW) was administered. In experiment 2, intact gilts (n = 7) were randomly assigned to 1 of 2 treatments (saline or 0.5 mg/kg BW of RF9) administered as a bolus injection and repeated over 2 replicates with 1 week between replicates. Four hours after RF9 treatment, GnRH (100 µg) was administered. Treatment with RFRP2 failed to suppress LH pulse frequency (1.16 ± 0.07 pulses/hour; P > 0.78), pulse amplitude (3.06 ± 0.45 ng/mL; P > 0.55), inter-pulse interval (53.97 ± 4.32 minutes; P > 0.68), or mean concentration (2.39 ± 0.27 ng/mL; P > 0.27). Treatment with SB75 reduced mean concentration of LH (P < 0.0001), but the suppressive effect did not differ between treatments (P > 0.53). Administration of RF9 stimulated a pulse-like release of LH that is comparable to an endogenous LH pulse. Treatment with RF9 increased (P = 0.003) mean concentrations of LH (0.51 ± 0.05 ng/mL) during the subsequent 4-hour period when compared to saline (0.26 ± 0.05 ng/mL) treated gilts. The GnRH-stimulated LH secretion following treatment with either saline or RF9 did not differ (4.34 ± 1.42 ng/mL; P = 0.82). While a direct suppressive effect of RFRP2 on LH secretion in the prepubertal gilt was not demonstrated, RF9-induced secretion of LH provides indirect evidence of RFRP involvement in the reproductive neuroendocrine axis of the pig. Sources of research support: USDA-NIFA-2011-67015.