| ACTH-receptor expression, regulation and role in adrenocortial tumor formation. | |
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MedLine Citation:
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PMID: 11248736 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The regulation of the ACTH-receptor gene is unique in that it is up-regulated by its own ligand, ACTH. Ligand-induced up-regulation of ACTH-receptor expression may be an important adaptive process directed towards optimizing adrenal responsiveness to ACTH in the context of physiological stress and the maintenance of metabolic homeostasis in which the adrenals play a pivotal role. Whereas enhancement by ligand-induced up-regulation permits a more efficient and rapid glucocorticoid response, negative feedback regulation of glucocorticoids in the hypothalamus and pituitary inhibits ACTH secretion and allows a balanced adrenal response to stress. Since the cloning of the promoter region of the ACTH receptor, considerable progress in the understanding of the regulatory processes has been made. The effects of ACTH on ACTH-receptor expression is dependent on cAMP, probably mediated through AP-1. The profound effect of three SF-1-binding sites in the ACTH-receptor promoter was demonstrated by deletion experiments. Conversely, ACTH-receptor expression can be suppressed by adrenal-specific transcription factors,like DAX-1. Despite an extensive search, no activating ACTH-receptor mutations have been found in adrenal tumors,excluding the ACTH receptor as a relevant oncogene in adrenal tumorigenesis. However, the ACTH receptor may act as a differentiation factor as suggested by LOH in adrenal carcinomas with an undifferentiated tumor type. In benign adrenal tumors, a strong correlation between ACTH-receptor expression and expression of P450 steroidogenic enzymes is evident. This close regulative relationship is lost in adrenal carcinoma, probably as a result of tumor dedifferentiation. Down-regulation of ACTH-receptor expression in normal and neoplastic tissue can be achieved by adrenostatic compounds such as aminoglutethimide and metyrapone. |
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Authors:
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F Beuschlein; M Fassnacht; A Klink; B Allolio; M Reincke |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: European journal of endocrinology / European Federation of Endocrine Societies Volume: 144 ISSN: 0804-4643 ISO Abbreviation: Eur. J. Endocrinol. Publication Date: 2001 Mar |
Date Detail:
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Created Date: 2001-03-15 Completed Date: 2001-04-26 Revised Date: 2009-11-03 |
Medline Journal Info:
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Nlm Unique ID: 9423848 Medline TA: Eur J Endocrinol Country: England |
Other Details:
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Languages: eng Pagination: 199-206 Citation Subset: IM |
Affiliation:
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Schwerpunkt Endokrinologie, Abteilung Innere Medizin II, Klinikum der Albert-Ludwigs-Universitat, Freiburg, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenal Cortex Neoplasms
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genetics,
metabolism*,
pathology* Animals Exons / genetics Gene Expression Regulation* / drug effects Humans Introns / genetics Loss of Heterozygosity Point Mutation / genetics Promoter Regions, Genetic / genetics RNA, Messenger / genetics, metabolism Receptors, Corticotropin / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/Receptors, Corticotropin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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