{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:43:34Z","timestamp":1787719414447,"version":"build-2784847793"},"reference-count":119,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The onset of puberty is a critical developmental milestone regulated by complex neuroendocrine networks that integrate genetic, metabolic, and environmental cues. Among the molecular systems coordinating this transition, neurotrophins\u2014including brain-derived neurotrophic factor (BDNF), nerve growth factor, neurotrophin-3, and neurotrophin-4\/5\u2014have emerged as important modulators of hypothalamic maturation and the activation of gonadotropin-releasing hormone (GnRH) neurons. Beyond their established roles in neuronal survival and differentiation, neurotrophins contribute to hypothalamic circuit plasticity, influence GnRH neuronal activity, and participate in the integration of metabolic and environmental signals relevant to reproductive maturation. Experimental studies, primarily based on animal and cellular models, demonstrate that BDNF and its receptor play a role in normal pubertal onset, whereas disruptions in neurotrophin signaling have been implicated in central precocious puberty, delayed puberty, and hypogonadotropic hypogonadism. In humans, available evidence is more limited and derives mainly from genetic studies, circulating neurotrophin measurements, and clinical observations. This review provides an integrative synthesis of current experimental and clinical data on neurotrophin-mediated regulation of pubertal timing, highlighting both physiological mechanisms and pathological conditions. While neurotrophins represent promising modulators at the intersection of neurodevelopment, metabolism, and reproduction, further longitudinal and translational human studies are required to define their diagnostic and therapeutic potential in pediatric endocrinology.<\/jats:p>","DOI":"10.3390\/cimb48010003","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T12:59:57Z","timestamp":1766149197000},"page":"3","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neurotrophic Control of Puberty: From Molecular Signaling to Disorders of Pubertal Timing"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7020-1471","authenticated-orcid":false,"given":"Roberto","family":"Paparella","sequence":"first","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"Iafrate","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Lucibello","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Bei","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Bernabei","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0857-6039","authenticated-orcid":false,"given":"Cinzia","family":"Fiorentini","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavinia","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pastore","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2404-2806","authenticated-orcid":false,"given":"Vittorio","family":"Maglione","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4766-7753","authenticated-orcid":false,"given":"Marcello","family":"Niceta","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Molecular Genetics and Functional Genomics, Ospedale Pediatrico Bambino Ges\u00f9, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-9715","authenticated-orcid":false,"given":"Marco","family":"Fiore","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC-CNR), c\/o Department of Sensory Organs, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1112-8096","authenticated-orcid":false,"given":"Sabrina","family":"Venditti","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Pucarelli","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, 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