{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:34:10Z","timestamp":1792809250751,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endometriosis is an oestrogen\u2010dependent disease in which endometrial\u2010like tissue grows outside the uterus in women of reproductive age. Accordingly, control of oestradiol (E2) levels is an effective treatment for endometriosis. Because gonadotropin\u2010releasing hormone (GnRH) is the main controller of E2 secretion, control of GnRH signalling by GnRH antagonism is an effective strategy for the treatment of sex hormone\u2010dependent diseases such as endometriosis. The purpose of the present study was to evaluate the effects of the potent, orally available and selective GnRH antagonist linzagolix on experimental endometriosis in rats and compare them with those of dienogest, which is used clinically to treat endometriosis. Experimental endometriosis was induced in female rats at the proestrus stage of the oestrous cycle via autotransplantation of endometrial tissue into the renal subcapsular space. Linzagolix significantly decreased cyst volumes compared with the control group at doses of 50\u2009mg\/kg or more. Indeed, a suppressive effect of dienogest on cyst volume was observed only at the highest dose evaluated (1\u2009mg\/kg). The effective concentration of linzagolix, calculated as the free form of the last\u2010observed drug concentration, was ~1\u2009\u03bcmol\/L in endometriosis model rats. The present study also reveals that linzagolix exerts a sustained inhibitory effect on E2 secretion, indicating that the suppressive effect on endometriosis cyst volumes could be attributed to its pharmacological suppression of GnRH signalling and serum E2 concentrations. Altogether, our findings indicate that linzagolix may be a useful therapeutic intervention for hormone\u2010dependent diseases including endometriosis.<\/jats:p>","DOI":"10.1111\/1440-1681.13778","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T02:48:10Z","timestamp":1682563690000},"page":"610-617","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Suppressive effects of linzagolix, a novel non\u2010peptide antagonist of gonadotropin\u2010releasing hormone receptors, in experimental endometriosis model rats"],"prefix":"10.1111","volume":"50","author":[{"given":"Motohiro","family":"Tezuka","sequence":"first","affiliation":[{"name":"Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.  Azumino Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumi","family":"Tsuchioka","sequence":"additional","affiliation":[{"name":"Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.  Azumino Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.  Azumino Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Kuramochi","sequence":"additional","affiliation":[{"name":"Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.  Azumino Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumiyoshi","family":"Kiguchi","sequence":"additional","affiliation":[{"name":"Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.  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