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Titolo:
EXPRESSION OF GLUCOCORTICOID RECEPTOR GENE ISOFORMS IN CORTICOTROPIN-SECRETING TUMORS
Autore:
DAHIA PLM; HONEGGER J; REINCKE M; JACOBS RA; MIRTELLA A; FAHLBUSCH R; BESSER GM; CHEW SL; GROSSMAN AB;
Indirizzi:
ST BARTHOLOMEWS HOSP,DEPT ENDOCRINOL LONDON EC1A 7BE ENGLAND ST BARTHOLOMEWS HOSP,DEPT ENDOCRINOL LONDON EC1A 7BE ENGLAND UNIV ERLANGEN NURNBERG,NEUROCHIRURG KLIN D-91054 ERLANGEN GERMANY KLINIKUM BAYER JULIUS MAXIMILIANS UNIV D-97080 WURZBURG GERMANY
Titolo Testata:
The Journal of clinical endocrinology and metabolism
fascicolo: 4, volume: 82, anno: 1997,
pagine: 1088 - 1093
SICI:
0021-972X(1997)82:4<1088:EOGRGI>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
PITUITARY-ADENOMAS; CUSHINGS-SYNDROME; MESSENGER-RNA; DIFFERENTIAL-DIAGNOSIS; MUTATIONS; PROOPIOMELANOCORTIN; HORMONE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
P.L.M. Dahia et al., "EXPRESSION OF GLUCOCORTICOID RECEPTOR GENE ISOFORMS IN CORTICOTROPIN-SECRETING TUMORS", The Journal of clinical endocrinology and metabolism, 82(4), 1997, pp. 1088-1093

Abstract

The molecular basis of Gushing's disease is not known. One of the most characteristic features of such tumors is their resistance to corticosteroid feedback at the pituitary level. We have hypothesized that abnormalities of the glucocorticoid receptor (GR) gene might play a rolein the development of Gushing's disease via an increase in the relative production of the nonligand-binding splice variant of the GR, GR beta, known to exert dominant negative effects over the ligand-binding isoform, GR alpha. Alternatively, a change in overall GR expression, ormutations of some functional domains of the GR gene, might be involved in the pathogenesis of corticotroph tumors. We studied 22 tumors (17pituitary ACTH-secreting tumors, 2 ectopic ACTH-producing tumors, 2 prolactinomas, and 1 nonfunctioning adenoma) and three normal pituitaries. RT-PCR was performed with primers specific to GR alpha and GR betacomplementary DNA, followed by Southern blotting using an internal probe, and the ratio of the two bands quantitated by densitometry. We also assessed the overall expression of GR relative to the message of both the POMC gene and a housekeeping gene. Single-strand conformation polymorphism analysis of the DNA-binding domain and splice junction region of the gene was also performed. GR alpha messenger RNA was expressed at 37.3-fold +/- 5.7 (range, 32 to 46) excess, as compared with theGR beta subform. This pattern was observed both in the tumor samples and in the normal pituitaries used as controls. A majority of the ACTH-secreting tumors (16/19), including the ectopic secretors, showed variable but increased overall GR expression, whereas 3 tumors showed an expression approximately equivalent to the normal controls; however, no correlation was found between these two groups and the response to the high-dose dexamethasone test, nor was there any correlation with tumor histology. No mutations were found in any of the tumors by PGR-single-strand conformation polymorphism analysis. In conclusion, althoughboth pituitary and ectopic ACTH-secreting tumors are at least partially glucocorticoid-resistant, no significant abnormalities in the relative expression of the two main GR subforms were observed in a series of such tumors. Additionally, mutations of regions critical to normal function of the receptor do not seem to be a frequent event in these tumors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 07:39:56