Cited by 1,102Hypothalamic control of reproductive hormonesNeuroendocrine regulation and behaviorEstrogen and related hormone effects

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Regulation of Kiss1 Gene Expression in the Brain of the Female Mouse

Smith, Jeremy T., Cunningham, Matthew J., Rissman, Emilie F., Clifton, Donald K, Steiner, Robert A.·2005·Endocrinology

DOI 10.1210/en.2005-0488

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Abstract

The Kiss1 gene encodes a family of neuropeptides called kisspeptins, which activate the receptor G protein-coupled receptor-54 and play a role in the neuroendocrine regulation of GnRH secretion. We examined whether estradiol (E2) regulates KiSS-1 in the forebrain of the female mouse by comparing KiSS-1 mRNA expression among groups of ovary-intact (diestrus), ovariectomized (OVX), and OVX plus E2-treated mice. In the arcuate nucleus (Arc), KiSS-1 expression increased after ovariectomy and decreased with E2 treatment. Conversely, in the anteroventral periventricular nucleus (AVPV), KiSS-1 expression was reduced after ovariectomy and increased with E2 treatment. To determine whether the effects of E2 on KiSS-1 are mediated through estrogen receptor (ER)alpha or ERbeta, we evaluated the effects of E2 in OVX mice that lacked functional ERalpha or ERbeta. In OVX mice that lacked functional ERalpha, KiSS-1 mRNA did not respond to E2 in either the Arc or AVPV, suggesting that ERalpha is essential for mediating the inhibitory and stimulatory effects of E2. In contrast, KiSS-1 mRNA in OVX mice that lacked functional ERbeta responded to E2 exactly as wild-type animals. Double-label in situ hybridization revealed that virtually all KiSS-1-expressing neurons in the Arc and AVPV coexpress ERalpha, suggesting that the effects of E2 are mediated directly through KiSS-1 neurons. We conclude that KiSS-1 neurons in the Arc, which are inhibited by E2, may play a role in the negative feedback regulation of GnRH secretion, whereas KiSS-1 neurons in the AVPV, which are stimulated by E2, may participate in the positive feedback regulation of GnRH secretion.

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Authors: Smith, J. T., Cunningham, M. J., Rissman, E. F., Clifton, D. K., & Steiner, R. A.
Affiliations: University of Washington (US)
University of Virginia (US)
Corresponding author: Steiner, Robert A.
ORCID: Cunningham, Matthew J.
Rissman, Emilie F.
Steiner, Robert A.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2005-09-01
Volume: 146
Issue: 9
Pages: 3686-3692
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2005-0488
OpenAlex: W1975890243
Cited by: 1,102
References: 50
Citations by year: 2026: 19 · 2025: 30 · 2024: 49 · 2023: 42 · 2022: 58 · 2021: 75 · 2020: 42 · 2019: 61 · 2018: 62 · 2017: 66 · 2016: 65 · 2015: 49 · 2014: 63 · 2013: 73 · 2012: 65
FWCI: 41.36
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
ResearchWorks at the University of Washington (University of Washington) (submittedVersion)
Funders: National Institutes of Health (5u54hd012629-31)
National Institute of Mental Health (R01 MH 57759, K02 MH-01349, K02MH001349, R01MH057759)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061517, R01 DK61517)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 27142, U54-HD-12629, R01HD027142)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Keywords: KISS1, kisspeptin, kisspeptin neurons, estradiol, estrogen receptor alpha, estrogen receptor beta, arcuate nucleus, anteroventral periventricular nucleus, GnRH secretion, negative feedback, positive feedback, ovariectomy, forebrain
MeSH terms: Animals, Arcuate Nucleus of Hypothalamus, Body Weight, Estrogens, Female, Mice, Inbred C57BL, Mice, Mutant Strains, Ovariectomy, Paraventricular Hypothalamic Nucleus, Proteins, RNA, Messenger, Estrogen Receptor alpha, Estrogen Receptor beta, Mice, Kisspeptins

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Regulation of Kiss1 Gene Expression in the Brain of the Female Mouse

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