Variation in Kisspeptin and RFamide-Related Peptide (RFRP) Expression and Terminal Connections to Gonadotropin-Releasing Hormone Neurons in the Brain: A Novel Medium for Seasonal Breeding in the Sheep
Open accessAbstract
Reproductive activity in sheep is seasonal, being activated by short-day photoperiods and inhibited by long days. During the nonbreeding season, GnRH secretion is reduced by both steroid-independent and steroid-dependent (increased response to estradiol negative feedback) effects of photoperiod. Kisspeptin (also known as metastin) and gonadotropin-inhibitory hormone (GnIH, or RFRP) are two RFamide neuropeptides that appear critical in the regulation of the reproductive neuroendocrine axis. We hypothesized that expression of kisspeptin and/or RFRP underlies the seasonal change in GnRH secretion. We examined kisspeptin and RFRP (protein and mRNA) expression in the brains of ovariectomized (OVX) ewes treated with estradiol (OVX+E) during the nonbreeding and breeding seasons. In OVX+E ewes, greater expression of kisspeptin and Kiss1 mRNA in the arcuate nucleus and lesser expression of RFRP (protein) in the dorsomedial nucleus of the hypothalamus were concurrent with the breeding season. There was also a greater number of kisspeptin terminal contacts onto GnRH neurons and less RFRP-GnRH contacts during the breeding season (compared with the nonbreeding season) in OVX+E ewes. Comparison of OVX and OVX+E ewes in the breeding and nonbreeding season revealed a greater effect of steroid replacement on inhibition of kisspeptin protein and Kiss1 mRNA expression during the nonbreeding season. Overall, we propose that the two RFamide peptides, kisspeptin and RFRP, act in concert, with opposing effects, to regulate the activity of GnRH neurons across the seasons, leading to the annual change in fertility and the cyclical seasonal transition from nonbreeding to breeding season.
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RFRP-3 neurons may affect puberty onset, seasonal cyclicity, and suppression of GnRH-induced gonadotropin release.
“may be involved in influencing the onset of puberty, the onset of cyclicity in seasonally reproductive mammals, and the suppression of GnRH-induced release of gonadotropins9,10.”
From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [9]
The Discussion (pp. 8–9) proposes that RFRP helps control seasonal breeding in ewes, and p. 2 reports that RFRP-3 inhibits gonadotropin secretion. The passages do not address puberty onset or establish suppression specifically of GnRH-induced gonadotropin release; searches for those terms found no such result. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn mammals, the pulsatile secretion of GnRH is reduced in the nonbreeding (anestrous) season, and the reactivation of the hypothalamic-pituitary-gonadal axis is dictated by a seasonal-dependent increase in kisspeptin expression and a concomitant reduction in Gonadotropin-inhibitory hormone (GnIH) production.
“In mammals, the pulsatile secretion of GnRH is reduced in the nonbreeding (anestrous) season, and the reactivation of the hypothalamic–pituitary–gonadal axis is dictated by a seasonal-dependent increase in kisspeptin expression and a concomitant reduction in Gonadotropin-inhibitory hormone (GnIH) production (26–28).”
From Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in <i>Platynereis</i> (2020) · cites this paper as [26]
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- Authors
- Smith, J. T., Coolen, L. M., Kriegsfeld, L. J., Sari, I. P., Jaafarzadehshirazi, M. R., Maltby, M., Bateman, K., Goodman, R. L., Tilbrook, A. J., Ubuka, T., Bentley, G. E., Clarke, I. J., & Lehman, M. N.
- Affiliations
- Monash University (AU)
- Western University (CA)
- University of California, Berkeley (US)
- Department of Animal Physiology (M.R.J.), School of Biology, University College of Science, University of Tehran, 14155 Tehran, Iran
- West Virginia University (US)
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-07-10
- Volume
- 149
- Issue
- 11
- Pages
- 5770-5782
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2584593
- OpenAlex
- W2038039689
- Cited by
- 387
- References
- 52
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 7 · 2022: 19 · 2021: 22 · 2020: 15 · 2019: 18 · 2018: 25 · 2017: 24 · 2016: 28 · 2015: 19 · 2014: 32 · 2013: 32 · 2012: 33
- FWCI
- 35.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD017864, HD17864, R01HD050470, HD 050470, R56HD017864)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- kisspeptin, RFamide-related peptides, GnRH neurons, seasonal reproduction, sheep, photoperiod, estradiol negative feedback, arcuate nucleus, dorsomedial hypothalamus, neuroendocrine regulation of reproduction, ovariectomy
- MeSH terms
- Animals, Brain, Estradiol, Female, Gene Expression Regulation, Gonadotropin-Releasing Hormone, Neurons, Neuropeptides, Ovariectomy, Reproduction, RNA, Messenger, Seasons, Sheep, Presynaptic Terminals, Tumor Suppressor Proteins
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