{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPROP1 is a pituitary‐specific homeodomain transcription factor that plays a central role in pituitary organogenesis by initiating cell fate specification in early pituitary progenitors. It is necessary for establishing the progenitor pool and subsequently activates the transcription of target genes, most notably POU1F1 (Pit‐1), which is essential for the differentiation of somatotropes, lactotropes, and thyrotropes. These findings indicate that PROP1 expression in early pituitary progenitors is critical for the generation of the entire spectrum of hormone‐producing cells of the anterior and intermediate lobes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in PROP1 are the most common genetic defects linked to combined pituitary hormone deficiency (CPHD) in humans. Patients with PROP1 mutations often exhibit a progressive decline in anterior pituitary hormone secretion—including growth hormone, thyroid-stimulating hormone, prolactin and gonadotropins—with some subsequently developing partial adrenal insufficiency. Furthermore, diverse pituitary morphologies have been documented among affected individuals, ranging from a hypoplastic anterior lobe in older subjects to transient pituitary enlargement in younger patients. These clinical observations underscore the importance of PROP1 in maintaining normal pituitary function over time."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, PROP1 functions through its DNA-binding and transactivation domains to control the expression of downstream genes. Detailed analyses have identified specific PROP1-binding elements within the human POU1F1 gene, and experimental studies demonstrate that PROP1 directly activates Pit-1 reporter constructs. Moreover, PROP1 activity is modulated through interactions with corepressors and other transcriptional regulators such as HESX1 and AES, and it may also interface with components of the Wnt/β-catenin pathway to influence pituitary cell lineage determination."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPROP1 is also vital for the regulation of the pituitary stem cell compartment; it promotes an epithelial-to-mesenchymal-like transition that enables progenitors to exit their niche and differentiate into hormone-producing cells in response to physiological demands. This function is key not only during embryonic development but also in orchestrating the adaptive responses of the adult anterior pituitary."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sushil Mody, Milton R Brown, John S Parks "}, {"type": "b", "children": [{"type": "t", "text": "The spectrum of hypopituitarism caused by PROP1 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Best Pract Res Clin Endocrinol Metab (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/beem.2002.0218"}], "href": "https://doi.org/10.1053/beem.2002.0218"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12464226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12464226"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "R Rodriguez, B Andersen "}, {"type": "b", "children": [{"type": "t", "text": "Cellular determination in the anterior pituitary gland: PIT-1 and PROP-1 mutations as causes of human combined pituitary hormone deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Minerva Endocrinol (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12717343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12717343"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shannon W Davis, Jessica L Keisler, María I Pérez-Millán, et al. "}, {"type": "b", "children": [{"type": "t", "text": "All Hormone-Producing Cell Types of the Pituitary Intermediate and Anterior Lobes Derive From Prop1-Expressing Progenitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2015-1862"}], "href": "https://doi.org/10.1210/en.2015-1862"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26812162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26812162"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Antje Böttner, Eberhard Keller, Jürgen Kratzsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2004-0661"}], "href": "https://doi.org/10.1210/jc.2004-0661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15472232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15472232"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Antonis Voutetakis, Maria Argyropoulou, Amalia Sertedaki, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "An uncommon phenotype with familial central hypogonadism caused by a novel PROP1 gene mutant truncated in the transactivation domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2005-0119"}], "href": "https://doi.org/10.1210/jc.2005-0119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15941866"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15941866"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Teresa C Vieira, Magnus R Dias da Silva, Janete M Cerutti, et al. 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