{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:38:52Z","timestamp":1761489532432,"version":"3.37.3"},"reference-count":121,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,1,12]],"date-time":"2015-01-12T00:00:00Z","timestamp":1421020800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","award":["ZIA HD 008737-13 to JHS"],"award-info":[{"award-number":["ZIA HD 008737-13 to JHS"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:sec><jats:label\/><jats:p>Animal studies in the 1980s suggested the existence of an ovarian hormone, termed gonadotropin surge\u2010inhibiting\/attenuating factor (GnSIF\/AF), that modulates pituitary secretion of luteinizing hormone (LH). Given the importance of identifying regulatory factors of the hypothalamic\u2010pituitary\u2010ovarian axis and the accumulating data suggesting its existence, we conducted a comprehensive literature search using PubMed, Web of Science, Scopus, and Embase to identify articles related to GnSIF\/AF. The search generated 161 publications, of which 97 were included in this study. Several attempts have been made to identify and characterize this hormone and several candidates have been identified, but the protein sequences of these putative GnSIF\/AF factors differ widely from one study to another. In addition, while the RF\u2010amide RFRP\u20103 is known foremost as a neuropeptide, some research supports an ovarian origin for this non\u2010steroidal hormone, thereby suggesting a role for RFRP\u20103 either as a co\u2010modulator of GnSIF\/AF or as a gonadotropin\u2010inhibiting factor in the hypothalamus (GnIH). Discovery of the KNDy neurons that modulate GnRH secretion, on the other hand, further encourages the search for substance(s) that modulate their activity and that indirectly affect LH secretion and the hypothalamic\u2010pituitary\u2010ovarian axis. While it has remained an elusive hormone, GnSIF\/AF holds many potential applications for contraception, in vitro fertilization, and\/or cancer as well as for understanding polycystic ovary syndrome, metabolic diseases, and\/or pubertal development. In this review, we rigorously examine the available evidence regarding the existence of GnSIF\/AF, previous attempts at its identification, limitations to its discovery, future directions of research, and potential clinical applications. <jats:italic>Mol. Reprod. Dev. 82: 2\u201316, 2015. \u00a9 2014 Wiley Periodicals, Inc<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mrd.22439","type":"journal-article","created":{"date-parts":[[2015,1,12]],"date-time":"2015-01-12T16:51:48Z","timestamp":1421081508000},"page":"2-16","source":"Crossref","is-referenced-by-count":4,"title":["Gonadotropin surge\u2010inhibiting\/attenuating factors: A review of current evidence, potential applications, and future directions for research"],"prefix":"10.1002","volume":"82","author":[{"given":"Mario G.","family":"Vega","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology St. Luke's\u2010Roosevelt Hospital New York City New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shvetha M.","family":"Zarek","sequence":"additional","affiliation":[{"name":"Program in Reproductive and Adult Endocrinology <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development National Institutes of Health 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