Cited by 404Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyRegulation of Appetite and Obesity

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KiSS-1 Messenger Ribonucleic Acid Expression in the Hypothalamus of the Ewe Is Regulated by Sex Steroids and Season

Smith, Jeremy T., Clay, Colin M., Caraty, Alain, Clarke, Iain J.·2007·Endocrinology

DOI 10.1210/en.2006-1435

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Abstract

The KiSS-1 gene encodes a family of peptides called kisspeptins, which are endogenous ligands for the G protein-coupled receptor GPR54. Kisspeptin function appears to be critical for GnRH secretion and the initiation of puberty. To test the hypothesis that steroid hormones regulate KiSS-1 mRNA expression in the ewe, we examined the brains of ovary-intact (luteal phase) and ovariectomized (OVX) ewes, as well as OVX ewes that received estradiol (E) or progesterone (P) replacement. KiSS-1 mRNA-expressing cells were predominantly located in the arcuate nucleus (ARC). Here, expression was increased after OVX but returned to the level of gonad-intact animals with E treatment. Treatment with P partially restored KiSS-1 expression toward gonad-intact levels. Double-label immunohistochemistry revealed that approximately 86% of kisspeptin-immunoreactive cells in the ARC are also P-receptor positive. Finally, we tested the hypothesis that KiSS-1 mRNA is lower during anestrus, due to a non-steroid-dependent seasonal effect. In OVX ewes, expression in the ARC was lower at the time of year corresponding to anestrus. We conclude that KiSS-1 expression in the ARC of the ewe brain is negatively regulated by chronic levels of E and P, suggesting that both steroids may exert negative feedback control on GnRH secretion through altered kisspeptin signaling. Furthermore, a seasonal alteration in KiSS-1 expression in the ARC of OVX ewes strongly suggests that kisspeptin is fundamentally involved in the control of seasonal changes in reproductive function.

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Authors: Smith, J. T., Clay, C. M., Caraty, A., & Clarke, I. J.
Affiliations: Monash University (AU)
Colorado State University (US)
Université de Tours (FR)
Corresponding author: Clarke, Iain J.
ORCID: Clay, Colin M.
Clarke, Iain J.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2007-03
Volume: 148
Issue: 3
Pages: 1150-1157
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2006-1435
OpenAlex: W2058782486
Cited by: 404
References: 73
Citations by year: 2026: 4 · 2025: 5 · 2024: 10 · 2023: 9 · 2022: 17 · 2021: 26 · 2020: 16 · 2019: 18 · 2018: 30 · 2017: 16 · 2016: 18 · 2015: 25 · 2014: 22 · 2013: 35 · 2012: 32
FWCI: 24.93
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Funders: Monash University
Medical Research Council
National Health and Medical Research Council
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: KISS1, kisspeptin, GPR54, hypothalamus, arcuate nucleus, ewes, sex steroids, estradiol, progesterone, ovariectomy, seasonal reproduction, anestrus, GnRH secretion, puberty, negative feedback, kisspeptin receptor
MeSH terms: Animals, Arcuate Nucleus of Hypothalamus, Estradiol, Female, Gene Expression Regulation, Hypothalamus, Ovariectomy, Progesterone, RNA, Messenger, Seasons, Gonadal Steroid Hormones, Sheep, Tissue Distribution, Tumor Suppressor Proteins

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KiSS-1 Messenger Ribonucleic Acid Expression in the Hypothalamus of the Ewe Is Regulated by Sex Steroids and Season

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