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Titolo:
Absence of mutations in the growth hormone (GH)-releasing hormone receptorgene in GH-secreting pituitary adenomas
Autore:
Salvatori, R; Thakker, RV; Lopes, MB; Fan, XG; Eswara, JR; Ellison, D; Lees, P; Harding, B; Yang, IM; Levine, MA;
Indirizzi:
Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol, Baltimore, MD 21287USA Johns Hopkins Univ Baltimore MD USA 21287 ocrinol, Baltimore, MD 21287USA Johns Hopkins Univ, Sch Med, Llyssa Ctr Mol & Cellular Endocrinol, Baltimore, MD 21287 USA Johns Hopkins Univ Baltimore MD USA 21287 crinol, Baltimore, MD 21287 USA Univ Oxford, Dept Clin Med, Oxford, England Univ Oxford Oxford EnglandUniv Oxford, Dept Clin Med, Oxford, England Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA USA Univ Virginia Charlottesville VA USA ept Pathol, Charlottesville, VA USA Southampton Gen Hosp, Dept Histopathol, Southampton SO9 4XY, Hants, England Southampton Gen Hosp Southampton Hants England SO9 4XY XY, Hants, England Southampton Gen Hosp, Dept Neurosurg, Southampton SO9 4XY, Hants, England Southampton Gen Hosp Southampton Hants England SO9 4XY XY, Hants, England Kyung Hee Univ, Dept Med, Seoul, South Korea Kyung Hee Univ Seoul South Korea Hee Univ, Dept Med, Seoul, South Korea Johns Hopkins Univ, Sch Med, Dept Paediat, Baltimore, MD USA Johns HopkinsUniv Baltimore MD USA Med, Dept Paediat, Baltimore, MD USA
Titolo Testata:
CLINICAL ENDOCRINOLOGY
fascicolo: 3, volume: 54, anno: 2001,
pagine: 301 - 307
SICI:
0300-0664(200103)54:3<301:AOMITG>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
THYROTROPIN-RELEASING-HORMONE; VASOACTIVE-INTESTINAL-PEPTIDE; SOMATOTROPH ADENOMAS; ELECTROPHORESIS DGGE; SOMATIC MUTATIONS; THYROID ADENOMAS; MESSENGER-RNA; G-PROTEIN; IN-VITRO; TUMORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Salvatori, R Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol, 1830 EMonument St 333, Baltimore, MD 21287 USA Johns Hopkins Univ 1830 E Monument St 333 Baltimore MD USA 21287
Citazione:
R. Salvatori et al., "Absence of mutations in the growth hormone (GH)-releasing hormone receptorgene in GH-secreting pituitary adenomas", CLIN ENDOCR, 54(3), 2001, pp. 301-307

Abstract

OBJECTIVE GH-releasing hormone (GHRH) is a potent stimulator of somatotroph cell proliferation and on secretion. GHRH acts via binding to a G-proteincoupled receptor (GPCR) (GHRH-R), that activates adenylyl cyclase (AC) andincreases 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 theintracellular 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 GNAS1 gene.

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Documento generato il 06/04/20 alle ore 07:38:02