{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T22:25:12Z","timestamp":1778106312305,"version":"3.51.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2006,8,1]],"date-time":"2006-08-01T00:00:00Z","timestamp":1154390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Premature ovarian failure (POF) is characterized by amenorrhea and high serum levels of follicle-stimulating hormone (FSH). POF causes female infertility and represents a substantial women\u2019s health risk affecting 1% of women by age 40. Although ovarian autoimmunity has been associated with POF, the identity of ovarian Ags recognized is unknown. In this study, we show that autoimmune-targeted disruption of the pituitary-ovarian axis leads to POF. Immunization of SWXJ female mice with the p215\u2013234 peptide derived from mouse inhibin-\u03b1 activates CD4+ T cells and induces experimental autoimmune oophoritis with a unique biphasic phenotype characterized by an early stage of enhanced fertility followed by a delayed stage of POF. Affected mice show high serum levels of inhibin-\u03b1-neutralizing Abs that prevent inhibin-mediated down-regulation of activin-induced pituitary FSH release. The loss of activin\/FSH down-regulation leads to prolonged metestrus-diestrus, superovulation, increased numbers of mature follicles, increased offspring, accelerated depletion of primordial follicles, and ultimately premature infertility. Thus, inhibin-\u03b1-targeted experimental autoimmune oophoritis is initiated by CD4+ Th1 T cells that stimulate B cells to produce inhibin-\u03b1-neutralizing Abs directly capable of mediating POF and transferring disease into naive recipients. Our inhibin-\u03b1 autoimmune model of POF shows how premature infertility may develop in the context of elevated FSH levels thereby closely mimicking the hallmark features of human POF.<\/jats:p>","DOI":"10.4049\/jimmunol.177.3.1988","type":"journal-article","created":{"date-parts":[[2014,4,24]],"date-time":"2014-04-24T16:59:02Z","timestamp":1398358742000},"page":"1988-1996","source":"Crossref","is-referenced-by-count":46,"title":["Autoimmune Targeted Disruption of the Pituitary-Ovarian Axis Causes Premature Ovarian Failure"],"prefix":"10.1093","volume":"177","author":[{"given":"Cengiz Z","family":"Altuntas","sequence":"first","affiliation":[{"name":"Department of Immunology, Lerner Research Institute, Cleveland Clinic , Cleveland, OH 44195"},{"name":"Department of Biology, Cleveland State University , Cleveland, OH 44115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin M","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Immunology, Lerner Research Institute, Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent K","family":"Tuohy","sequence":"additional","affiliation":[{"name":"Department of Immunology, Lerner Research Institute, Cleveland Clinic , Cleveland, OH 44195"},{"name":"Department of Biology, Cleveland State University , Cleveland, OH 44115"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2006,8,1]]},"reference":[{"key":"2025032807094200900_R1","first-page":"604","volume-title":"Obstet. 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