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However, the biology linking\n                    <jats:italic>LIN28B<\/jats:italic>\n                    with these traits is still poorly understood. With our study, we sought to elucidate the mechanisms behind the\n                    <jats:italic>LIN28B<\/jats:italic>\n                    associations, with a special focus on studying\n                    <jats:italic>LIN28B<\/jats:italic>\n                    function at the hypothalamic-pituitary (HP) axis that is ultimately responsible for pubertal onset. Using CRISPR-Cas9 technology, we first generated\n                    <jats:italic>lin28b<\/jats:italic>\n                    knockout (KO) zebrafish. Compared to controls, the\n                    <jats:italic>lin28b<\/jats:italic>\n                    KO fish showed both accelerated growth tempo, reduced adult size and increased expression of mitochondrial genes during larval development. Importantly, data from the knockout zebrafish\u00a0models and adult humans imply that\n                    <jats:italic>LIN28B<\/jats:italic>\n                    expression has potential to affect gene expression in the HP axis. Specifically, our results suggest that\n                    <jats:italic>LIN28B<\/jats:italic>\n                    expression correlates positively with the expression of\n                    <jats:italic>ESR1<\/jats:italic>\n                    in the hypothalamus and\n                    <jats:italic>POMC<\/jats:italic>\n                    in the pituitary. Moreover, we show how the pubertal timing advancing allele (T) for rs7759938 at the\n                    <jats:italic>LIN28B<\/jats:italic>\n                    locus associates with higher testosterone levels in the\u00a0UK Biobank data. Overall, we provide novel evidence that\n                    <jats:italic>LIN28B<\/jats:italic>\n                    contributes to the regulation of sex hormone pathways, which might help explain why the gene associates with several distinct traits.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-54475-6","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T06:37:14Z","timestamp":1575268634000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["LIN28B affects gene expression at the hypothalamic-pituitary axis and serum testosterone levels"],"prefix":"10.1038","volume":"9","author":[{"given":"Jaakko T.","family":"Leinonen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Pennonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leevi","family":"Lehtonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nella","family":"Junna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taru","family":"Tukiainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1189-5132","authenticated-orcid":false,"given":"Pertti","family":"Panula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Wid\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,2]]},"reference":[{"key":"54475_CR1","doi-asserted-by":"publisher","unstructured":"Day, F. 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