| Growth hormone internalization in mitochondria decreases respiratory chain activity. | |
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MedLine Citation:
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PMID: 20016135 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Growth hormone (GH) is a signaling molecule regulating cell proliferation, differentiation and metabolism via activation of specific cell surface receptors and subsequent triggering of signal transduction pathways. This is associated with GH/GH receptor internalization and accumulation of GH in several subcellular compartments, including mitochondria. To assess the functional relevance of such mitochondrial accumulation, we first confirmed the occurrence of mitochondrial GH uptake ex vivo as early as 10 min after (125)I-GH injection to the rats. We next showed that intact (125)I-GH accumulates in mitochondrial fractions in vitro in a specific, rapid and saturable manner with an apparent affinity (K(d)) of 1.44 nM. At the electron-microscopic level, immunoreactive GH density within mitochondria increased after in vitro hormone incubation, without any modification of the sub-mitochondrial distribution pattern. The presence of GH in the inter-membrane space and at the inner membrane seen by electron microscopy was confirmed by SDS-PAGE and autoradiography after mitochondrial fractioning thus suggesting the involvement of GH in the respiration control. To test this hypothesis further, we performed polarographic and spectrophotometric assays on isolated mitochondria. These assays pointed to a direct, selective and dose-dependent effect of GH on the inhibition of succinate dehydrogenase and cytochrome C oxidase activities. The latter inhibition was in contrast with indirect, GH receptor-initiated stimulation of cytochrome C oxidase activity observed in GH-treated whole BRL cells transfected to express this receptor. Altogether, these data show that GH is specifically imported in mitochondria, where it operates a direct metabolic effect, independently of cell surface receptors and signal transduction. |
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Authors:
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Dominique Ardail; Aude Debon; C?cile Perret-Vivancos; Marie-Claire Biol-N'Garagba; Slavika Krantic; Peter E Lobie; G?rard Morel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-17 |
Journal Detail:
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Title: Neuroendocrinology Volume: 91 ISSN: 1423-0194 ISO Abbreviation: Neuroendocrinology Publication Date: 2010 |
Date Detail:
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Created Date: 2010-01-21 Completed Date: 2010-03-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0035665 Medline TA: Neuroendocrinology Country: Switzerland |
Other Details:
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Languages: eng Pagination: 16-26 Citation Subset: IM |
Copyright Information:
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Copyright 2009 S. Karger AG, Basel. |
Affiliation:
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IFR 41, CNRS UMR 5123, Physiologie Int?grative Cellulaire et Mol?culaire, Universit? de Lyon, Villeurbanne, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Electron Transport / physiology* Electron Transport Complex IV / metabolism Growth Hormone / metabolism* Iodine Radioisotopes Liver / metabolism, ultrastructure Male Mitochondria, Liver / metabolism*, ultrastructure Mitochondrial Membranes / metabolism, ultrastructure Rats Rats, Wistar Receptors, Somatotropin / metabolism Succinate Dehydrogenase / metabolism Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Iodine Radioisotopes; 0/Receptors, Somatotropin; 9002-72-6/Growth Hormone; EC 1.3.99.1/Succinate Dehydrogenase; EC 1.9.3.1/Electron Transport Complex IV |
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