{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T21:00:01Z","timestamp":1790542801940,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,3,4]]},"abstract":"<jats:p>\n                    Melatonin is produced nocturnally by the pineal gland and is a neurochemical representation of time. It regulates neuroendocrine target tissues through G-protein-coupled receptors, of which MT\n                    <jats:sub>1<\/jats:sub>\n                    is the predominant subtype. These receptors are transiently expressed in several fetal and neonatal tissues, suggesting distinct roles for melatonin in development and that specific developmental cues define time windows for melatonin sensitivity. We have investigated MT\n                    <jats:sub>1<\/jats:sub>\n                    gene expression in the rat pituitary gland. MT\n                    <jats:sub>1<\/jats:sub>\n                    mRNA is confined to the pars tuberalis region of the adult pituitary, but in neonates extends into the ventral pars distalis and colocalizes with luteinizing hormone \u03b2-subunit (LH\u03b2) expression. This accounts for the well documented transient sensitivity of rat gonadotrophs to melatonin in the neonatal period. Analysis of an upstream fragment of the rat MT\n                    <jats:sub>1<\/jats:sub>\n                    gene revealed multiple putative response elements for the transcription factor pituitary homeobox-1 (Pitx-1), which is expressed in the anterior pituitary from Rathke's pouch formation. A Pitx-1 expression vector potently stimulated expression of both MT\n                    <jats:sub>1<\/jats:sub>\n                    -luciferase and LH\u03b2-luciferase reporter constructs in COS-7 cells. Interestingly, transcription factors that synergize with Pitx-1 to\n                    <jats:italic>trans<\/jats:italic>\n                    -activate gonadotroph-associated genes did not potentiate Pitx-1-induced MT\n                    <jats:sub>1<\/jats:sub>\n                    -luciferase activity. Moreover, the transcription factor, early growth response factor-1, which is induced by gonadotrophin-releasing hormone (GnRH) and\n                    <jats:italic>trans<\/jats:italic>\n                    -activates LH\u03b2 expression, attenuated Pitx-1-induced MT\n                    <jats:sub>1<\/jats:sub>\n                    -luciferase activity. Finally, pituitary MT\n                    <jats:sub>1<\/jats:sub>\n                    gene expression was 4-fold higher in\n                    <jats:italic>hypogonadal<\/jats:italic>\n                    (\n                    <jats:italic>hpg<\/jats:italic>\n                    ) mice, which do not synthesize GnRH, than in their wild-type littermates. These data suggest that establishment of a mature hypothalamic GnRH input drives the postnatal decline in pituitary MT\n                    <jats:sub>1<\/jats:sub>\n                    gene expression.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0436184100","type":"journal-article","created":{"date-parts":[[2003,3,4]],"date-time":"2003-03-04T13:36:00Z","timestamp":1046784960000},"page":"2831-2835","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":38,"title":["Gonadotrophin-releasing hormone drives melatonin receptor down-regulation in the developing pituitary gland"],"prefix":"10.1073","volume":"100","author":[{"given":"Jonathan D.","family":"Johnston","sequence":"first","affiliation":[{"name":"School of Biological Sciences, University of Aberdeen, Aberdeen AB24 5UA, United Kingdom; School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, United Kingdom; and Molecular Neuroendocrinology Group, Rowett Research Institute, Aberdeen AB21 9SB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Messager","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Aberdeen, Aberdeen AB24 5UA, United Kingdom; School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, United Kingdom; and Molecular Neuroendocrinology Group, Rowett Research Institute, Aberdeen AB21 9SB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis J. P.","family":"Ebling","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Aberdeen, Aberdeen AB24 5UA, United Kingdom; School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, United Kingdom; and Molecular Neuroendocrinology Group, Rowett Research Institute, Aberdeen AB21 9SB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda M.","family":"Williams","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Aberdeen, Aberdeen AB24 5UA, United Kingdom; School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, United Kingdom; and Molecular Neuroendocrinology Group, Rowett Research Institute, Aberdeen AB21 9SB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry","family":"Barrett","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Aberdeen, Aberdeen AB24 5UA, United 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