Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

OBJECTIVE: GH-releasing hormone (GHRH) is a potent stimulator of somatotroph cell proliferation and GH secretion. GHRH acts via binding to a G-protein coupled receptor (GPCR) (GHRH-R), that activates adenylyl cyclase (AC) and increases growth and function of somatotroph cells. Indeed, a subset (30--40%) of somatotrophic adenomas contain somatic mutations of the GNAS1 gene that encodes the alpha subunit of the G-protein (G(s)alpha) that stimulates AC. As activating mutations of other GPCRs cause development of endocrine tumours, we hypothesized that somatic activating mutations of the GHRH-R might provide the molecular basis for somatotroph cell proliferation in a subset of human GH-secreting pituitary adenomas. DESIGN: We analysed genomic DNA isolated from 26 somatotrophinomas, 17 of which lacked activating mutations in the GNAS1 gene. We individually amplified via polymerase chain reaction all 13 coding exons and the exon-intron boundaries of the GHRH-R gene. We used denaturing gradient gel electrophoresis to search for abnormalities in exons 1 through 11. Abnormally migrating bands were subjected to direct sequencing. Exons 12 and 13, encoding for the intracellular C-terminal domain, were subjected to direct sequencing. RESULTS: Mutations were not detected in any of the tumours, but a rare polymorphism in codon 225 corresponding to the third transmembrane domain (V225I) was discovered. CONCLUSIONS: GHRH-R mutations are absent or rare in somatotrophinomas, and other mechanisms must explain the somatotroph cell proliferation in the adenomas that lack activating mutations in the GNAS1 gene.

Type

Journal article

Journal

Clin Endocrinol (Oxf)

Publication Date

03/2001

Volume

54

Pages

301 - 307

Keywords

Adenoma, Animals, CHO Cells, Cricetinae, DNA, Neoplasm, Germ-Line Mutation, Growth Hormone, Humans, Mutagenesis, Site-Directed, Neoplasm Proteins, Pituitary Neoplasms, Receptors, Neuropeptide, Receptors, Pituitary Hormone-Regulating Hormone