Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release

Abstract

In seasonal breeders, reproduction is synchronised by day length via the pineal hormone melatonin. In short winter days (short day, SD), the Syrian hamster displays a complete gonadal atrophy together with a marked reduction in expression of kisspeptins (Kp), a family of potent hypothalamic stimulators of GNRH neurons. Both central and peripheral acute injections of Kp have been reported to activate the gonadotropic axis in mammals. The aim of this study was to determine if and how peripheral administration of Kp54 could restore gonadal function in photo-inhibited hamsters. Testicular activity of hamsters kept in SD was reactivated by two daily i.p. injections of Kp54 but not by chronic subcutaneous delivery of the same peptide via mini-pumps. Acute i.p. injection of Kp54-induced FOS (c-Fos) expression in a large number of GNRH neurons and pituitary gonadotrophs together with a strong increase in circulating testosterone. The activation of pituitary cells by Kp was inhibited by preadministration of the GNRH receptor antagonist acyline. Altogether, our results demonstrate that peripheral Kp54 activates the gonadotropic axis by stimulating GNRH release and indicate that an appropriate protocol of long-term systemic Kp administration can recrudesce a photo-inhibited reproductive axis.

Effects of Pinealectomy and Short Day Lengths on Reproduction and Neuronal RFRP-3, Kisspeptin, and GnRH in Female Turkish Hamsters

“…In contrast to Syrian hamsters, kisspeptin is reduced in the AVPV and increased in the ARC of SD male and female Siberian hamsters, compared to LD animals (Greives et al, 2007; Mason et al, 2007, respectively); this effect is abolished in hamsters unresponsive to short day lengths (Greives et al, 2007). Kisspeptin replacement restores the LD phenotype in photoregressed male Syrian hamsters (Revel et al, 2006a; Ansel et al, 2011) but not male Siberian hamsters (Greives et al, 2008), with the latter finding presumably due to kisspeptin receptor downregulation following continuous peptide infusion. In the present investigation, SDs decreased AVPV kisspeptin cell area but not cell number in Turkish hamsters.…”

“…In Syrian hamsters and prairie voles, GnRH mRNA production is unchanged by photoperiod (Kriegsfeld et al, 2000; Ronchi et al, 1992b), whereas GnRH-ir cell numbers are increased (Kriegsfeld and Nelson, 1999; Rochi et al, 1992a), suggesting that reproductive regression results from inhibited GnRH release, rather than reduced synthesis. Likewise, pituitary responsiveness to GnRH is unchanged in SD relative to LD animals across rodent species (Pickard and Silverman, 1979; Ansel et al, 2011; Kriegsfeld et al, 1999), further implicating reduced GnRH signaling in the transition to reproductive quiescence and its maintenance. In the mPOA, in contrast, the total number of immunoreactive cells was not affected by melatonin manipulation, but cell size was decreased in reproductively quiescent hamsters.…”

“…In male and female Siberian hamsters, kisspeptin-ir is reduced in the AVPV and increased in the ARC of SD compared to LD hamsters (Greives et al, 2007; Mason et al, 2007). Kisspeptin replacement reactivates the reproductive axis and breaks photoinhibition in male Syrian hamsters (Revel et al, 2006a; Ansel et al, 2011). …”

Seasonal control of gonadotropin-inhibitory hormone (GnIH) in birds and mammals

“…The role of kisspeptin in seasonal breeding has principally been explored in Syrian and Siberian hamsters [3,33,34,60,79] and sheep [14,18,31,32,56,95,96]. Across species, kisspeptin is generally elevated during the breeding season and suppressed following exposure to inhibitory photoperiods or appropriately timed melatonin administration.…”

Molecular basis for regulating seasonal reproduction in vertebrates

“…Kisspeptin stimulates GnRH release via G protein-coupled receptor GPR54 located at the surface of GnRH neurons resulting in activation of the HPG axis (Oakley et al 2009). In LD breeding rodents, melatonin inhibits secretion of kisspeptin from the hypothalamic arcuate nucleus (Revel et al 2006, Ansel et al 2010, and administration of kisspeptin restores the reproductive activity in SD conditions (Revel et al 2006, Ansel et al 2011. RFRP-1 and -3 peptides were originally identified as mammalian orthologs of gonadotropin inhibitory hormone (GnIH) that inhibits the HPG axis in birds (Tsutsui et al 2013).…”