Relationship of neuropeptide FF receptors with pubertal maturation of gilts

Authors: Thorson, Jennifer; HEIDORN, NEELY - University Of Georgia; RYU, VITALY - Washington State University; CZAJA, KRZYSZTOF - University Of Georgia; Nonneman, Danny - Dan; Barb, Claude; Hausman, Gary; Rohrer, Gary; PREZOTTO, LIGIA - North Dakota State University; MCCOSH, RICHARD - West Virginia University; Wright, Elane; WHITE, BRETT - University Of Nebraska; Freking, Bradley - Brad; Oliver, William; HILEMAN, STANLEY - West Virginia University; Lents, Clay

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/18/2017
Publication Date: 1/28/2017
Publication URL: https://handle.nal.usda.gov/10113/5700738
Citation: Thorson, J.F., Heidorn, N.L., Ryu, V., Czaja, K., Nonneman, D.J., Barb, C.R., Hausman, G.J., Rohrer, G.A., Prezotto, L.D., McCosh, R.B., Wright-Johnson, E.C., White, B.R., Freking, B.A., Oliver, W.T., Hileman, S.M., Lents, C.A. 2017. Relationship of neuropeptide FF receptors with pubertal maturation of gilts. Biology of Reproduction. 96(3):617-634. doi:10.1095/biolreprod.116.144998

Interpretive Summary: Replacement pigs for the breeding herd are called gilts. Nearly a third of gilts selected as replacements are culled from the herd due to infertility, including failure to reach puberty. ARS scientists at Clay Center, Nebraska, identified differences in the DNA sequence of a gene called NPFF receptor 2 (NPFFR2) that were associated with differences in age at puberty of pigs. Scientists discovered that the expression of NPFFR2 in reproductive tissues was markedly different in pigs with different stages of pubertal development. They discovered that when NPFFR2 was activated that it could alter the secretion of hormones that regulate reproductive function. This new information will be used by scientists to develop methods to minimize the number of pigs that fail to reach puberty and thereby reduce the number of animals that are required for the breeding herd.

Technical Abstract: Mechanisms governing the timing of puberty in pigs are poorly understood. A genome-wide association study for age at first estrus in pigs identified candidate genes including NPFFR2, which is a putative receptor for RFamide-related peptides (RFRP). RFRP has been shown to negatively regulate secretion of reproductive hormones from hypothalamic and pituitary tissue of pigs in culture. Here, the porcine NPFFR2 gene was further screened and four potentially functional variants were identified to be associated with age at first estrus in pigs (1,288 gilts). The organization of RFRP in the porcine hypothalamus was determined to be greatest in the paraventricular and dorsomedial nuclei with RFRP fibers in the lateral hypothalamic area. There were marked changes in expression of NPFF receptors in the anterior pituitary gland and hypothalamus of gilts beginning with the peripubertal period. The hypothesis that NPFF receptor function is related to secretin of luteinizing hormone (LH) in gilts was tested with various NPFF receptor ligands. The NPFF receptor antagonist RF9 stimulated a pulse-like release of LH in prepubertal gilts. The putative NPFF receptor agonist RFRP3 modestly suppressed LH pulses in ovariectomized (OVX) prepubertal gilts. A porcine specific RFRP2 failed to have an effect on LH secretion in OVX prepubertal gilts despite its high degree of homology to avian gonadotropin-inhibitory hormone. Results indicate that an RFRP system is present in the pig and that NPFFR2 is important for pubertal onset in gilts. It is not entirely clear if this regulation involves major control of LH secretion of another unknown mechanism.