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ISSN 0188-9796 (Print)

2008, Number 3

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Rev Endocrinol Nutr 2008; 16 (3)

High prevalence of a polymorphism in codon 422 of the 64 releasing hormone receptor gene in Mexican patients with acromegaly

Sosa E, Mendoza V, Espinosa-de-los-Monteros AL, Ovalle A, Hernández I, Guinto G, Molina M, Mercado M

Language: Spanish
References: 28
Page: 114-119
PDF size: 131.56 Kb.


ABSTRACT

Background: The lack of a unifying etiologic explanation for all GH-secreting tumors has prompted a search that goes beyond the GSP oncogene. Somatotroph cell proliferation and hormonal secretion depend upon a proper GHRH signaling through specific heptahelic receptors. Activating mutations of other, related heptahelic receptors such as TSH receptor form the basis for hyperfunctioning thyroid adenomas. Objective: We sought to search for potentially activating mutations of the GHRH-R gene in a large number of GH-secreting tumors and in an equivalent number of non-functioning adenomas. Study design and methods: Forty four GH-secreting pituitary adenomas and 17 non-functioning pituitary tumors (NFT) were examined for the presence of molecular changes in exons 3, 7 and 13 of the GHRH-R gene by PCR and direct sequencing. Patients were prospectively followed clinically and biochemically for up to 6 years after surgery. Results: A heterozygous, single base substitution resulting in an ATG to ACG change at codon 422 was found in 54% of GH-secreting adenomas, 23% of NFT and 40% in PBMNC obtained from healthy subjects. The presence of such base change was not related to any clinical or biochemical feature of the patients, nor did it predict outcome. Conclusions: Although the prevalence of codon 422 ATG to ACT base change is high in our Mexican population with acromegaly, its presence in a significant proportion of non-functioning tumors and in controls, makes it unlikely that it participates in a significant manner in the pathogenesis of somatotropinomas.


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