ArticleThe Journal of clinical endocrinology and metabolism2022
Inhibiting Kiss1 Neurons With Kappa Opioid Receptor Agonists to Treat Polycystic Ovary Syndrome and Vasomotor Symptoms.
Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The trial behind it
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Who cites it
11 citing papers in PubMed, 39 citations in OpenAlex.
- Neurokinin receptor antagonists for vasomotor symptoms: from KNDy neurons to clinical translation.Nature reviews. Endocrinology · 2026Review
- Article
- POMC neurons control fertility through differential signaling of MC4R in kisspeptin neurons.eLife · 2025Article
- A New Hope for Woman with Vasomotor Symptoms: Neurokinin B Antagonists.Journal of clinical medicine · 2025Review
- Article
- Targeted inhibition of kisspeptin neurons reverses hyperandrogenemia and abnormal hyperactive LH secretion in a preclinical mouse model of polycystic ovary syndrome.Human reproduction (Oxford, England) · 2024Article
- Polycystic Ovary Syndrome: Past, Present and Future.Journal of clinical medicine · 2023Article
- Polycystic ovary syndrome: pathophysiology and therapeutic opportunities.BMJ medicine · 2023Review
- 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
- The role of gonadotropin-releasing hormone neurons in polycystic ovary syndrome.Journal of neuroendocrinology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
contextRecent evidence suggests that vasomotor symptoms (VMS) or hot flashes in the postmenopausal reproductive state and polycystic ovary syndrome (PCOS) in the premenopausal reproductive state emanate from the hyperactivity of Kiss1 neurons in the hypothalamic infundibular/arcuate nucleus (KNDy neurons).
objectiveWe demonstrate in 2 murine models simulating menopause and PCOS that a peripherally restricted kappa receptor agonist (PRKA) inhibits hyperactive KNDy neurons (accessible from outside the blood-brain barrier) and impedes their downstream effects.
designCase/control.
settingAcademic medical center.
participantsMice.
interventionsAdministration of peripherally restricted kappa receptor agonists and frequent blood sampling to determine hormone release and body temperature.
main outcome measuresLH pulse parameters and body temperature.
resultsFirst, chronic administration of a PRKA to bilaterally ovariectomized mice with experimentally induced hyperactivity of KNDy neurons reduces the animals' elevated body temperature, mean plasma LH level, and mean peak LH per pulse. Second, chronic administration of a PRKA to a murine model of PCOS, having elevated plasma testosterone levels and irregular ovarian cycles, suppresses circulating levels of LH and testosterone and restores normal ovarian cyclicity.
conclusionThe inhibition of kisspeptin neuronal activity by activation of kappa receptors shows promise as a novel therapeutic approach to treat both VMS and PCOS in humans.
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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.