{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:09:16Z","timestamp":1780384156561,"version":"3.54.1"},"reference-count":45,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01 HD082314"],"award-info":[{"award-number":["R01 HD082314"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/04870-9"],"award-info":[{"award-number":["2022\/04870-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pubertal onset is driven by the reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, a process orchestrated by a complex interplay of stimulatory and inhibitory factors and influenced strongly by genetic regulation. In this study, we assessed the expression patterns of 3 genes associated with central precocious puberty (CPP) in humans\u2014Mkrn3, Dlk1, and Mecp2\u2014across pubertal maturation in male and female mice. Hypothalamic regions were collected for mRNA quantification by reverse transcription and real time quantitative polymerase chain reaction and protein measurement by Western blot for all 3 genes; in addition, serum samples were used for Dlk1 quantification by enzyme-linked immunosorbent assay. Hypothalamic levels of Mkrn3 mRNA and protein, a well-established inhibitor of pubertal onset, were high in early postnatal life and declined prior to puberty onset, consistent with its role in suppressing HPG axis activation. In contrast, Dlk1 mRNA and protein levels were higher in adults than younger mice\u2014an unexpected finding since loss of DLK1 expression advances puberty onset. Conversely, serum Dlk1 decreased progressively with age, suggesting a role for peripheral Dlk1 in pubertal regulation. Mecp2, a key epigenetic regulator implicated recently in puberty regulation, had lower hypothalamic mRNA levels after PND10, whereas protein levels remained unchanged, possibly reflecting splice variant\u2013specific expression or post-transcriptional regulation. These distinct age-dependent expression patterns suggest that Mkrn3 and Mecp2 likely contribute primarily to central HPG axis regulation, whereas Dlk1 originating peripherally may act as a central regulator of puberty. Defining these trajectories offers insights into the molecular control of pubertal timing and potential therapeutic targets for pubertal disorders.<\/jats:p>","DOI":"10.1210\/jendso\/bvag086","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T11:46:18Z","timestamp":1775216778000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Mkrn3<\/i>\n                    ,\n                    <i>Dlk1,<\/i>\n                    and\n                    <i>Mecp2<\/i>\n                    have distinct hypothalamic expression patterns across pubertal maturation in male and female mice"],"prefix":"10.1210","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8547-6507","authenticated-orcid":false,"given":"Flavia R","family":"Tinano","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115, USA"},{"name":"Division of Endocrinology, Department of Internal Medicine, University of Sao Paulo Medical School, University of S\u00e3o Paulo , Sao Paulo 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinthia G","family":"Meireles","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delanie B","family":"Macedo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115, USA"},{"name":"Integrated Medical Care Center, Center for Health Sciences, University of Fortaleza (Unifor) , Fortaleza 60811-905 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Boris","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney","family":"Pereira","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Magnuson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Abreu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rona S","family":"Carroll","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia","family":"Latronico","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, University of Sao Paulo Medical School, University of S\u00e3o Paulo , Sao Paulo 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8237-0704","authenticated-orcid":false,"given":"Ursula B","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115, 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