| Distinctive roles for prolactin and growth hormone in the activation of signal transducer and activator of transcription 5 in pancreatic islets of langerhans. | |
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MedLine Citation:
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PMID: 15142985 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although the beta-cells of the pancreatic islets of Langerhans express both prolactin (PRL) and GH receptors, we have observed that PRL is considerably more effective than GH in the up-regulation of islet function in vitro. This study examined whether differences in the activation of the Janus kinase 2/signal transducer and activator of transcription (STAT) 5 signaling pathway by these closely related receptors may be involved in this disparity. The activation of STAT5B by PRL was biphasic, with an initial peak within 30 min, a nadir between 1 and 3 h, and prolonged activation after 4 h. In contrast, the response to GH was transient for 1 h. The importance of the long-term activation of STAT5B by PRL was supported by the similar dose response curves for STAT5B activation and the PRL-induced increases in insulin secretion and islet cell proliferation. Because the pulsatile secretion of GH affects its actions in other target tissues, the ability of pretreatment with either hormone to affect subsequent stimulation was also examined. Surprisingly, the response to PRL was inhibited by prior exposure for less than 3 h to either PRL or GH and disappeared with a longer pretreatment with either hormone. Similar to other tissues, the response to GH was inhibited by any length of prior exposure to GH. However, pretreatment with PRL had no effect. These experiments are the first demonstration of the transient desensitization of the PRL receptor by either PRL or GH pretreatment in any tissue and the desensitization of GH stimulation in islet cells. These observations provide insight into the mechanisms that regulate the desensitization of these receptors and, more importantly, allow the long-term activation of STAT5B by the PRL receptor. These results may apply to other members of the cytokine superfamily of receptors. We also demonstrate that the increase in islet cell proliferation required continuous stimulation with PRL, whereas the smaller effect with GH occurred with either continuous or pulsatile stimulation. In summary, this study demonstrates that islets are sensitive to the temporal pattern of stimulation by these hormones and provides a new basis for understanding their physiological roles in the regulation of islet function. |
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Authors:
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T Clark Brelje; Laurence E Stout; Nicholas V Bhagroo; Robert L Sorenson |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2004-05-13 |
Journal Detail:
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Title: Endocrinology Volume: 145 ISSN: 0013-7227 ISO Abbreviation: Endocrinology Publication Date: 2004 Sep |
Date Detail:
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Created Date: 2004-08-23 Completed Date: 2004-09-28 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 4162-75 Citation Subset: AIM; IM |
Affiliation:
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Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, 6-160 Jackson Hall, 321 Church Street SE, Minneapolis, Minnesota 55455, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Division / drug effects Cell Line, Tumor DNA-Binding Proteins / metabolism* Growth Hormone / pharmacology, physiology* Insulinoma Islets of Langerhans / cytology, drug effects, physiology* Janus Kinase 2 Kinetics Milk Proteins* Pancreatic Neoplasms Phosphorylation Prolactin / pharmacology, physiology* Protein-Tyrosine Kinases / metabolism Proto-Oncogene Proteins* Rats STAT5 Transcription Factor Signal Transduction / drug effects, physiology* Trans-Activators / metabolism* Tyrosine / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK33655/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Milk Proteins; 0/Proto-Oncogene Proteins; 0/STAT5 Transcription Factor; 0/Stat5b protein, rat; 0/Trans-Activators; 55520-40-6/Tyrosine; 9002-62-4/Prolactin; 9002-72-6/Growth Hormone; EC 2.7.1.112/Jak2 protein, rat; EC 2.7.10.1/Janus Kinase 2; EC 2.7.10.1/Protein-Tyrosine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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