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KiSS-1 Messenger Ribonucleic Acid Expression in the Hypothalamus of the Ewe Is Regulated by Sex Steroids and Season
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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“In animal models, the KISS1 neurons appear to mediate sex steroid feedback effects in the hypothalamus.58,59”
From Pubertal development and regulation (2016) · cites this paper as [59]
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Metadata
- 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.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2007-03
- Volume
- 148
- Issue
- 3
- Pages
- 1150-1157
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- 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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