Central RFRP-3 Stimulates LH Secretion in Male Mice and Has Cycle Stage–Dependent Inhibitory Effects in Females

• Published in: Endocrinology (Philadelphia) Vol. 158; no. 9; pp. 2873 - 2883
• Main Authors: Ancel, Caroline, Inglis, Megan A, Anderson, Greg M
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.09.2017; Oxford University Press
• Subjects: 17β-Estradiol; Androgens; Animals; Endocrinology; Estrous Cycle - drug effects; Estrous Cycle - metabolism; Female; Females; Gonadotropins; Gonadotropins - secretion; Infusions, Intraventricular; Kiss1 protein; Luteinizing hormone; Luteinizing Hormone - secretion; Male; Males; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuropeptides - administration & dosage; Neuropeptides - pharmacology; Ovariectomy; Pituitary (anterior); Receptors, G-Protein-Coupled - genetics; Receptors, Kisspeptin-1; Reproduction (biology); Rodents; Secretion; Sex; Sex Characteristics; Sex hormones
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2016-1902

Abstract RFamide-related peptide (RFRP)-3 is a neuropeptide thought to play an inhibitory role in the regulation of reproduction in various mammalian species, although some stimulatory effects have been reported. To date, the effects of RFRP-3 on gonadotropin secretion have been scarcely studied in mice. The aim of the current study was to characterize the effect of RFRP-3 administration on gonadotropin secretion in male and female mice. Adult intact and castrated male mice received acute central injections of 0.5 to 5 nmol of RFRP-3, and luteinizing hormone (LH) concentration was assayed in tail-tip blood samples. RFRP-3 had a dose-dependent stimulatory effect on LH secretion when administered centrally to both intact and castrated mice, and this effect was diminished when RFRP-3 was administered to kisspeptin receptor knockout mice. In female mice, central RFRP-3 had an inhibitory effect on LH secretion when administered at the time of the preovulatory LH surge in intact mice, or of an estradiol-induced LH surge in ovariectomized mice. Conversely, central RFRP-3 administration had no effect on LH levels in intact diestrus or ovariectomized, low-dose estradiol-implanted mice. Finally, peripheral administration of RFRP-3 to intact males and to females at the time of the preovulatory LH surge or during diestrus had no effect on LH secretion. Taken together, these results provide a detailed description of sex- and cycle stage–dependent effects of RFRP-3 on gonadotrophin secretion in mice. Moreover, it appears that the stimulatory effects are mediated in part by the receptor for kisspeptin, a potent stimulator of the reproductive axis. This work investigates the effect of RFRP-3 on LH secretion in intact and castrated male and female mice. The results show sex-dependent differences in the effects.