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Pathogenesis of pituitary tumors

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Abstract

Pituitary adenomas may hypersecrete hormones (including prolactin, growth hormone and adrenocorticotropic hormone, and rarely follicle-stimulating hormone, luteinizing hormone or TSH) or may be nonfunctional. Despite their high prevalence in the general population, these tumors are invariably benign and exhibit features of differentiated pituitary cell function as well as premature proliferative arrest. Pathogenesis of dysregulated pituitary cell proliferation and unrestrained hormone hypersecretion may be mediated by hypothalamic, intrapituitary and/or peripheral factors. Altered expression of pituitary cell cycle genes, activation of pituitary selective oncoproteins or loss of pituitary suppressor factors may be associated with aberrant growth factor signaling. Considerable information on the etiology of these tumors has been derived from transgenic animal models, which may not accurately and universally reflect human tumor pathophysiology. Understanding subcellular mechanisms that underlie pituitary tumorigenesis will enable development of tumor aggression markers as well as novel targeted therapies.

Key Points

  • Pituitary cell growth and hormone synthesis are controlled by hypothalamic, intrapituitary and peripheral factors

  • Pituitary tumors arising from differentiated hormone-expressing cells are commonly encountered and are invariably benign

  • Adenomas may secrete one or more hormones including prolactin, growth hormone, adrenocorticotropic hormone, glycoprotein gonadotroph subunits or hormones, or TSH; most are nonsecreting with no obvious peripheral clinical phenotype

  • The pathogenetic mechanisms that underlie pituitary tumorigenesis may be genetic or epigenetic and result in cell cycle dysregulation, signaling defects or loss of tumor suppressor factors

  • Rarely, patients present with pituitary tumors that are components of familial genetic syndromes

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Figure 1: Cascade of pituitary tumorigenesis.
Figure 2: Intracellular signaling associated with pituitary cell proliferation and transformation.

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Layal Chaker, Salman Razvi, … Robin P. Peeters

Change history

  • 01 April 2011

    In the version of this article initially published online, there was an error in the penultimate sentence of page 4. This sentence should have read 'Pttg was isolated from rat pituitary tumor cells by differential RNA display with normal pituitary glands, and is also induced by the E2F transcription factor in the pituitary gland.45,46' The error has been corrected for the print, HTML and PDF versions of the article.

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Melmed, S. Pathogenesis of pituitary tumors. Nat Rev Endocrinol 7, 257–266 (2011). https://doi.org/10.1038/nrendo.2011.40

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