| Functional interaction of bone morphogenetic protein and growth hormone releasing peptide in adrenocorticotropin regulation by corticotrope cells. | |
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MedLine Citation:
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PMID: 21742013 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Mechanisms by which GHRP stimulates ACTH release in corticotrope cells were investigated using mouse corticotrope AtT20 cells by focusing on the biological activity of BMP-4. GHRP-2 increased ACTH and cAMP secretion by AtT20 cells; however, its effects were less potent than the effects of CRH. BMP-4 suppressed basal ACTH production and POMC transcription, and the inhibition of endogenous BMP receptor signaling led to an increase in ACTH production. Of note, BMP-4 suppressed ACTH production and POMC-promoter activity induced by CRH more efficaciously than that induced by GHRP-2. BMP-4 had no significant effect on cAMP synthesis induced by CRH or GHRP-2. Stimulation with CRH, but not GHRP-2, activated ERK1/2, p38, SAPK/JNK and Akt phosphorylation, in which CRH-induced phosphorylation of ERK and p38 was suppressed by BMP-4. GHRP-2-induced ACTH secretion was not affected by inhibitors of ERK, p38 and Akt pathways, which effectively suppressed CRH-induced ACTH release. Blockage of the cAMP-PKA pathway reversed CRH- as well as GHRP-2-induced ACTH secretion. Furthermore, the inhibition of ERK and p38 significantly reduced cAMP synthesis induced by CRH but not by GHRP-2. Thus, CRH activates ACTH production through ERK and p38 pathways in addition to the cAMP-PKA pathway, which is also activated downstream of MAPK. On the other hand, GHRP-2-induced ACTH production was predominantly linked to the cAMP-PKA pathway. Moreover, CRH and GHRP-2 upregulated BMP receptor signaling, while BMP-4, CRH and GHRP-2 had no significant effect on the expression level of GHSR. In addition, GHRP-2 suppressed the expression of Smad7, which is an inhibitor of the BMP-Smad1/5/8 pathway. Collectively, the results revealed a functional interaction between GHRP-2 and BMP signaling, in which endogenous BMP may act as an autoregulatory system in controlling ACTH production. |
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Authors:
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Naoko Tsukamoto; Fumio Otsuka; Tomoko Miyoshi; Kenichi Inagaki; Eri Nakamura; Tomohiro Terasaka; Masaya Takeda; Toshio Ogura; Yasumasa Iwasaki; Hirofumi Makino |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-1 |
Journal Detail:
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Title: Molecular and cellular endocrinology Volume: - ISSN: 1872-8057 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7500844 Medline TA: Mol Cell Endocrinol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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