GNAS imprinting and pituitary tumors

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Evidence from in vitro studies and naturally occurring human diseases indicate that several endocrine cells, and particularly somatotrophs, recognize cAMP as a growth factor. Accordingly, mutations of the α subunit of the stimulatory G protein gene (GNAS) leading to the constitutive activation of adenylyl cyclase (the so-called gsp oncogene) have been found in a significant proportion of GH-secreting pituitary adenomas. GNAS maps within a complex region known to have more than one imprinted genes. Indeed, GNAS locus gives rise to several transcripts, all resulting from splicing of alternative first exons to exon 2 of the Gsα gene by a parent-specific methylation pattern of most of its different promoters. This complex tissue-specific imprinting control results in a near-exclusive expression of Gsα from the maternal allele in specific endocrine tissues, including the pituitary. Due to the monoallelic origin of Gsα in normal pituitary gsp mutations occur on a maternal allele in order to have a phenotypic effect in both sporadic GH-secreting adenomas and those associated with the McCune-Albright syndrome. Moreover, this imprinted expression pattern appears to be relaxed in the majority of tumors negative for gsp that show biallelic expression of Gsα transcript. Interestingly, the clinical phenotype of gsp negative tumors containing high levels of Gsα mRNA and protein is similar to that characterizing gsp positive tumors. Therefore, genetic and epigenetic alterations of the GNAS gene, with subsequent dysregulation of the cAMP pathway, appear, to date, the only molecular hallmark of most GH-secreting adenomas.

Original languageEnglish
Pages (from-to)15-18
Number of pages4
JournalMolecular and Cellular Endocrinology
Issue number1-2
Publication statusPublished - Sep 2010


  • GH-secreting pituitary adenomas
  • GNAS
  • Imprinting
  • Pathogenesis

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry


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