Document Detail


Cortisol-secreting adrenal adenomas express 11beta-hydroxysteroid dehydrogenase type-2 gene yet possess low 11beta-HSD2 activity.
MedLine Citation:
PMID:  11288760     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: 11beta-hydroxysteroid dehydrogenase Type-2 (11beta-HSD2) is an unidirectional enzyme that catalyzes the conversion of glucocorticoid hormones cortisol and corticosterone (B) into their corresponding inactive forms, cortisone, and 11-dehydrocorticosterone (DH-B). We have provided evidence that 11beta-HSD2 is expressed as messenger RNA (mRNA) and protein in human adrenocortical cells, where its activity is inhibited in vitro by the main glucocorticoid agonists, adrenocorticotropic hormone (ACTH) and angiotensin-II. It seemed worthwhile, therefore, to study the gene expression and activity of 11beta-HSD2 in cortisol-secreting adrenocortical adenomas. METHODS: Three adrenal adenomas that produced Cushing syndrome were recruited. Three normal adrenal glands were obtained from patients who underwent unilateral nephrectomy with ipsilateral adrenalectomy for renal cancer. 11beta-HSD2 gene expression was studied by reverse transcriptionpolymerase chain reaction (RT-PCR) in adenoma and normal adrenocortical tissue. Cortisol, B, cortisone, and DH-B production by adenoma and adrenal slices in vitro was assayed by quantitative high-performance liquid chromatography (HPLC), and the activity of 11beta-HSD2 was evaluated by measuring the conversion of [3H]-cortisol to [3H]-cortisone. RESULTS: RT-PCR allowed the detection of the 11beta-HSD2 mRNA in the three adrenal adenomas and normal adrenal cortices examined. Under basal conditions, adenoma slices secreted higher amounts of cortisol and B, but markedly lower amounts of cortisone and DH-B than adrenal slices. ACTH raised cortisol and B production from both specimens, and it lowered cortisone and DH-B yield. The level basal conversion of [3H]-cortisol to [3H]-cortisone was notably less in adenomas than in adrenals, and ACTH decreased it in both tissues. CONCLUSIONS: Collectively, our findings indicate that cortisol-secreting adrenal adenomas express the 11beta-HSD2 gene, but the activity of the enzyme is suppressed in adenomas when compared with the normal adrenal cortex. We advance the hypothesis that the elevated local concentration of steroid hormones that occur in adenomas down-regulates 11beta-HSD2 activity, thereby contributing to their abnormal steroidogenic function.
Authors:
G Mazzocchi; F Aragona; L K Malendowicz; L Gottardo; G G Nussdorfer
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of investigative medicine : the official publication of the American Federation for Clinical Research     Volume:  49     ISSN:  1081-5589     ISO Abbreviation:  J. Investig. Med.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-04-05     Completed Date:  2001-05-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9501229     Medline TA:  J Investig Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  191-4     Citation Subset:  IM    
Affiliation:
Department of Human Anatomy and Physiology, School of Medicine, University of Padua, Italy.
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenase Type 2
Adenoma / enzymology*,  secretion
Adrenal Gland Neoplasms / enzymology*,  secretion
Adrenocorticotropic Hormone / pharmacology
Adult
Angiotensin II / pharmacology
Gene Expression Regulation, Enzymologic
Humans
Hydrocortisone / secretion*
Hydroxysteroid Dehydrogenases / genetics*,  metabolism
Chemical
Reg. No./Substance:
11128-99-7/Angiotensin II; 50-23-7/Hydrocortisone; 9002-60-2/Adrenocorticotropic Hormone; EC 1.1.-/Hydroxysteroid Dehydrogenases; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2; EC 1.1.1.146/HSD11B2 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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