ArticleEndocrinology2015
Positive, but not negative feedback actions of estradiol in adult female mice require estrogen receptor α in kisspeptin neurons.
Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 159 citations in OpenAlex.
- A protocol for physiologic LH surge induction in gonad intact female mice.Endocrinology · 2026Article
- Phase-dependent changes in serum kisspeptin and irisin levels across the menstrual cycle in healthy women.Journal of endocrinological investigation · 2026Article
- Kisspeptin fiber and receptor distribution analysis suggests its potential role in central sensorial processing and behavioral state control.Journal of neuroendocrinology · 2025Article
- Identification of an ionic mechanism for ERα-mediated rapid excitation in neurons.Science advances · 2024Article
- Role of Membrane Estrogen Receptor Alpha on the Positive Feedback of Estrogens on Kisspeptin and GnRH Neurons.eNeuro · 2024Article
- Estrogen receptor-α signaling in tanycytes lies at the crossroads of fertility and metabolism.Metabolism: clinical and experimental · 2024Article
- Anti-Müllerian Hormone: A Molecular Key to Unlocking Polycystic Ovary Syndrome?Seminars in reproductive medicine · 2024Review
- Reproductive function and behaviors: an update on the role of neural estrogen receptors alpha and beta.Frontiers in endocrinology · 2024Review
- KNDy Neurons of the Hypothalamus and Their Role in GnRH Pulse Generation: an Update.Endocrinology · 2023Review
- Article
- Characterization of MicroRNA expression profiles in the ovarian tissue of goats during the sexual maturity period.Journal of ovarian research · 2023Article
- Sex difference in developmental changes in visualized Kiss1 neurons in newly generated Kiss1-Cre rats.The Journal of reproduction and development · 2023Article
- Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice.Nature communications · 2023Article
- The molecular phenotype of kisspeptin neurons in the medial amygdala of female mice.Frontiers in endocrinology · 2023Article
- Hypothalamic-Pituitary-Gonadal Axis Disorders Impacting Fertility in Both Sexes and the Potential of Kisspeptin-Based Therapies to Treat Them.Handbook of experimental pharmacology · 2023Review
- Definition of the estrogen negative feedback pathway controlling the GnRH pulse generator in female mice.Nature communications · 2022Article
- Targeting KNDy neurons to control GnRH pulses.Current opinion in pharmacology · 2022Review
- Invited review: Translating kisspeptin and neurokinin B biology into new therapies for reproductive health.Journal of neuroendocrinology · 2022Review
- Impaired steroid hormone feedback in polycystic ovary syndrome: Evidence from preclinical models for abnormalities within central circuits controlling fertility.Clinical endocrinology · 2022Review
- Neuroendocrine control of gonadotropin-releasing hormone: Pulsatile and surge modes of secretion.Journal of neuroendocrinology · 2022Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Hypothalamic kisspeptin (Kiss1) neurons express estrogen receptor α (ERα) and exert control over GnRH/LH secretion in female rodents. It has been proposed that estradiol (E2) activation of ERα in kisspeptin neurons in the arcuate nucleus (ARC) suppresses GnRH/LH secretion (negative feedback), whereas E2 activation of ERα in kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) mediates the release of preovulatory GnRH/LH surges (positive feedback). To test these hypotheses, we generated mice bearing kisspeptin cell-specific deletion of ERα (KERαKO) and treated them with E2 regimens that evoke either negative or positive feedback actions on GnRH/LH secretion. Using negative feedback regimens, as expected, E2 effectively suppressed LH levels in ovariectomized (OVX) wild-type (WT) mice to the levels seen in ovary-intact mice. Surprisingly, however, despite the fact that E2 regulation of Kiss1 mRNA expression was abrogated in both the ARC and AVPV of KERαKO mice, E2 also effectively decreased LH levels in OVX KERαKO mice to the levels seen in ovary-intact mice. Conversely, using a positive feedback regimen, E2 stimulated LH surges in WT mice, but had no effect in KERαKO mice. These experiments clearly demonstrate that ERα in kisspeptin neurons is required for the positive, but not negative feedback actions of E2 on GnRH/LH secretion in adult female mice. It remains to be determined whether the failure of KERαKO mice to exhibit GnRH/LH surges reflects the role of ERα in the development of kisspeptin neurons, in the active signaling processes leading to the release of GnRH/LH surges, or both.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.