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

Jeremy T. Smith, Lique M. Coolen, Lance J. Kriegsfeld, Ika P. Sari, Mohammad R. Jaafarzadehshirazi, Matthew Maltby, Katherine Bateman, Robert L. Goodman, Alan J. Tilbrook, Takayoshi Ubuka, George E. Bentley, Iain J. Clarke, Michael N. Lehman

    Research output: Contribution to journalArticle

    262 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)5770-5782
    Number of pages13
    JournalEndocrinology
    Volume149
    Issue number11
    DOIs
    Publication statusPublished - 2008 Nov

    Fingerprint

    Kisspeptins
    Gonadotropin-Releasing Hormone
    Breeding
    Sheep
    Neurons
    Brain
    Steroids
    Photoperiod
    Messenger RNA
    Estradiol
    Mediodorsal Thalamic Nucleus
    RFamide peptide
    Arcuate Nucleus of Hypothalamus
    Proteins
    Neuropeptides
    Gonadotropins
    Hypothalamus
    Fertility
    Hormones

    ASJC Scopus subject areas

    • Endocrinology

    Cite this

    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. / Smith, Jeremy T.; Coolen, Lique M.; Kriegsfeld, Lance J.; Sari, Ika P.; Jaafarzadehshirazi, Mohammad R.; Maltby, Matthew; Bateman, Katherine; Goodman, Robert L.; Tilbrook, Alan J.; Ubuka, Takayoshi; Bentley, George E.; Clarke, Iain J.; Lehman, Michael N.

    In: Endocrinology, Vol. 149, No. 11, 11.2008, p. 5770-5782.

    Research output: Contribution to journalArticle

    Smith, JT, Coolen, LM, Kriegsfeld, LJ, Sari, IP, Jaafarzadehshirazi, MR, Maltby, M, Bateman, K, Goodman, RL, Tilbrook, AJ, Ubuka, T, Bentley, GE, Clarke, IJ & Lehman, MN 2008, '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', Endocrinology, vol. 149, no. 11, pp. 5770-5782. https://doi.org/10.1210/en.2008-0581
    Smith, Jeremy T. ; Coolen, Lique M. ; Kriegsfeld, Lance J. ; Sari, Ika P. ; Jaafarzadehshirazi, Mohammad R. ; Maltby, Matthew ; Bateman, Katherine ; Goodman, Robert L. ; Tilbrook, Alan J. ; Ubuka, Takayoshi ; Bentley, George E. ; Clarke, Iain J. ; Lehman, Michael N. / 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. In: Endocrinology. 2008 ; Vol. 149, No. 11. pp. 5770-5782.
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    abstract = "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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    AU - Coolen, Lique M.

    AU - Kriegsfeld, Lance J.

    AU - Sari, Ika P.

    AU - Jaafarzadehshirazi, Mohammad R.

    AU - Maltby, Matthew

    AU - Bateman, Katherine

    AU - Goodman, Robert L.

    AU - Tilbrook, Alan J.

    AU - Ubuka, Takayoshi

    AU - Bentley, George E.

    AU - Clarke, Iain J.

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