title: RFamide-related peptide-3 (RFRP-3) suppresses sexual maturation in a eusocial mammal.
abstract: Neuroendocrine mechanisms underlying social inhibition of puberty are not well understood. Here, we use a model exhibiting the most profound case of pubertal suppression among mammals to explore a role for RFamide-related peptide-3 [RFRP-3; mammalian ortholog to gonadotropin-inhibitory hormone (GnIH)] in neuroendocrine control of reproductive development. Naked mole rats (NMRs) live in sizable colonies where breeding is monopolized by two to four dominant animals, and no other members exhibit signs of puberty throughout their lives unless they are removed from the colony. Because of its inhibitory action on the reproductive axis in other vertebrates, we investigated the role of RFRP-3 in social reproductive suppression in NMRs. We report that RFRP-3 immunofluorescence expression patterns and RFRP-3/GnRH cross-talk are largely conserved in the NMR brain, with the exception of the unique presence of RFRP-3 cell bodies in the arcuate nucleus (Arc). Immunofluorescence comparisons revealed that central expression of RFRP-3 is altered by reproductive status, with RFRP-3 immunoreactivity enhanced in the paraventricular nucleus, dorsomedial nucleus, and Arc of reproductively quiescent NMRs. We further observed that exogenous RFRP-3 suppresses gonadal steroidogenesis and mating behavior in NMRs given the opportunity to undergo puberty. Together, our findings establish a role for RFRP-3 in preserving reproductive immaturity, and challenge the view that stimulatory peptides are the ultimate gatekeepers of puberty.
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.
authors.forename: Diana E
authors.initials: DE
authors.lastname: Peragine
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.
authors.forename: Martha
authors.initials: M
authors.lastname: Pokarowski
authors.affiliation: Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.|Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mendoza-Viveros
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.
authors.forename: Ashlyn
authors.initials: A
authors.lastname: Swift-Gallant
authors.affiliation: Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.|Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.
authors.forename: Hai-Ying M
authors.initials: HM
authors.lastname: Cheng
authors.affiliation: Department of Integrative Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720.
authors.forename: George E
authors.initials: GE
authors.lastname: Bentley
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada; melissa.holmes@utoronto.ca.|Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Holmes
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D004302:Dorsomedial Hypothalamic Nucleus / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D007276:Injections, Intraventricular; D059648:Kisspeptins / Q000378:metabolism; D008032:Limbic System / Q000378:metabolism*; D008297:Male; D019577:Mole Rats / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D010053:Ovary / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis / Q000097:blood; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology; D012741:Sexual Maturation / Q000187:drug effects / Q000502:physiology*; D012934:Social Isolation; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood
chemical_list: D059648:Kisspeptins; D009479:Neuropeptides; C416987:RFamide peptide; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011374:Progesterone
keywords: GnIH; RFRP-3; eusocial; naked mole rat; puberty