Nonhormonal target for endometriosis

Sarah Crunkhorn
Nature reviews. Drug discovery · 2021 · vol. 20(10) , pp. 740 · doi:10.1038/d41573-021-00150-3 · PMID:34475540 · W3198760111
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⚙ AI-generated summary by claude@2026-06+body, 2026-06-19 ⓘ

NPSR1 variants are associated with endometriosis in humans and macaques, and NPSR1 inhibition reduced monocyte inflammation and pain in mouse models.

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This paper examined nonhormonal genetic and mechanistic contributors to endometriosis by interrogating a previously reported susceptibility linkage signal on chromosome 7p13-15. The authors identified variants in NPSR1, the neuropeptide S receptor 1 gene, associated with endometriosis in humans and rhesus macaques, and found NPSR1-positive infiltrating monocytes in endometriosis patient peritoneal fluid. In vitro, pharmacologic inhibition of NPSR1 with SHA 68R blocked monocyte proinflammatory signaling and chemotaxis, and in mouse models it reduced peritoneal inflammatory cell infiltration and abdominal pain. The article (as a review/discussion) does not present patient-level clinical efficacy data and instead focuses on target identification and preclinical validation, with the major limitation being translation from models to humans. This paper is centrally about endometriosis—highlighting NPSR1 as a nonhormonal treatment target supported by human and primate genetics, patient immune-cell observations, and mouse functional experiments.

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- IN BRIEF Nonhormonal target for endometriosis Current treatment for endometriosis involves surgery or hormonal therapies, and more tolerable approaches are urgently needed. By further interrogating their previously reported linkage signal for endometriosis on chromosome 7p13-15, Tapmeier et al. identify variants of NPSR1, the gene encoding neuropeptide S receptor 1, to be associated with endometriosis in humans and rhesus macaques. Infiltrating monocytes highly positive for NPSR1 were identified in peritoneal fluid from patients with endometriosis. Inhibition of NPSR1 using SHA 68R blocked monocyte proinflammatory signalling and chemotaxis in vitro, and significantly reduced peritoneal inflammatory cell infiltrate and abdominal pain in mouse models of endometriosis. Access options Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription 27,99 € / 30 days cancel any time Subscribe to this journal Receive 12 print issues and online access 251,40 € per year only 20,95 € per issue Rent or buy this article Prices vary by article type from$1.95 to$39.95 Prices may be subject to local taxes which are calculated during checkout Nature Reviews Drug Discovery 20, 740 (2021) doi: https://doi.org/10.1038/d41573-021-00150-3 References Tapmeier, T. et al. Neuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis. Sci. Transl Med. 13, eabd6469 (2021)

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endometriosis

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europepmc
last seen: 2026-06-28T06:08:18.748782+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
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