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The hypothalamic gonadotropin-inhibitory hormone (GnIH) was shown to be decreased in the early prepubertal stage, suggesting the role of GnIH on pubertal onset. Here, we investigated whether thyroid dysfunction affects pubertal onset in female mice <jats:italic>via<\/jats:italic> GnIH regulation. Hypothyroidism showed delayed pubertal onset with increased GnIH expression and reduced pituitary-gonadal activity. Remarkably, knockout of GnIH prevented the effect of hypothyroidism to delay the pubertal onset, resulting in indistinguishable pubertal timing in GnIH-knockout female mice between control and hypothyroidism-induced group, indicating that increased GnIH expression induced by hypothyroidism may lead to delayed puberty. In contrast, hyperthyroidism led to a decrease in GnIH expression, however pubertal onset was normal, implying further reduction of the inhibitory GnIH had little effect on the phenotypical change. Critically, thyroid hormone suppressed GnIH expression in hypothalamic explants and GnIH neurons expressed thyroid hormone receptors to convey the thyroid status. Moreover, the thyroid status highly regulated the chromatin modifications of <jats:italic>GnIH<\/jats:italic> promoter, H3acetylation and H3K9tri-methylation. These findings indicate a novel function of GnIH to mediate HPT-HPG interactions that contribute to proper pubertal development.<\/jats:p>","DOI":"10.1038\/s41598-017-01183-8","type":"journal-article","created":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T11:56:18Z","timestamp":1492084578000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status"],"prefix":"10.1038","volume":"7","author":[{"given":"Mika","family":"Kiyohara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Lee","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Tsutsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,21]]},"reference":[{"issue":"Suppl 3","key":"1183_CR1","doi-asserted-by":"publisher","first-page":"U25","DOI":"10.1530\/eje.0.151U025","volume":"151","author":"G Morreale de Escobar","year":"2004","unstructured":"Morreale de Escobar, G., Obregon, M. 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