{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T14:31:47Z","timestamp":1784903507856,"version":"3.55.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,3,18]]},"abstract":"<jats:p>Precocious puberty of cerebral origin is a poorly understood disorder of human sexual development, brought about by the premature activation of those neurons that produce luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling sexual maturation. An increased production of transforming growth factor \u03b1 (TGF\u03b1) in the hypothalamus has been implicated in the mechanism underlying both normal and precocious puberty. We have now used two gene delivery systems to target TGF\u03b1 overexpression near LHRH neurons in immature female rats. Fibroblasts infected with a retroviral construct in which expression of the human TGF\u03b1 gene is constitutively driven by the phosphoglycerate kinase promoter, or transfected with a plasmid in which TGF\u03b1 expression is controlled by an inducible metallothionein promoter, were transplanted into several regions of the hypothalamus. When the cells were in contact with LHRH nerve terminals or in the vicinity of LHRH perikarya, sexual maturation was accelerated. These results suggest that precocious puberty of cerebral origin may result from a focal disorder of TGF\u03b1 production within the confines of the LHRH neuron microenvironment.<\/jats:p>","DOI":"10.1073\/pnas.94.6.2735","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:39Z","timestamp":1027679499000},"page":"2735-2740","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":55,"title":["Targeting transforming growth factor \u03b1 expression to discrete loci of the neuroendocrine brain induces female sexual\u2009precocity"],"prefix":"10.1073","volume":"94","author":[{"given":"Florence","family":"Rage","sequence":"first","affiliation":[{"name":"Division of Neuroscience, Oregon Regional Primate Research Center\/Oregon Health Sciences University, Beaverton, OR 97006; Molecular Neurogenetic Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; Vanderbilt University Medical 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