Document Detail


Somatostatin receptor sst2 gene transfer in human prolactinomas in vitro: impact on sensitivity to dopamine, somatostatin and dopastatin, in the control of prolactin secretion.
MedLine Citation:
PMID:  22348806     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: As prolactinomas fail to respond to dopamine agonist (DA) in 10-20% of cases, we hypothesized that somatostatin subtype 2 receptor (sst2) overexpression in DA-resistant prolactinomas may enhance suppression of prolactine (PRL) using chimeric agonist (dopastatin) that simultaneously binds sst2 and the dopamine subtype 2 receptor (D2DR).
DESIGN AND METHODS: PRL suppression by octreotide, sst5 agonist, sst2-D2DR agonist (BIM-23A760 dopastatin) and cabergoline was assessed in primary cultures of seven DA-resistant prolactinomas overexpressing sst2.
RESULTS: sst2 was effectively overexpressed via adenoviral expression in prolactinomas (38.1±7.4 vs. 0.1±0.1 copy/copy β-Gus) and induced octreotide sst2-mediated PRL suppression that remained lower than that induced by DA. BIM-23A760 inhibited PRL similarly to cabergoline both in the control and sst2-expressing cells. Antagonist experiments confirmed predominant dopaminergic effect in dopastatin activity.
CONCLUSION: sst2 was successfully overexpressed in prolactinomas. However BIM-23A760 was unable to enhance PRL suppression underlining a predominant dopaminergic contribution in its action.
Authors:
Thomas Cuny; Amira Mohamed; Thomas Graillon; Catherine Roche; Céline Defilles; Anne-Laure Germanetti; Bettina Couderc; Dominique Figarella-Branger; Alain Enjalbert; Anne Barlier; Alexandru Saveanu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-14
Journal Detail:
Title:  Molecular and cellular endocrinology     Volume:  355     ISSN:  1872-8057     ISO Abbreviation:  Mol. Cell. Endocrinol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-03-26     Completed Date:  2012-07-11     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  7500844     Medline TA:  Mol Cell Endocrinol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  106-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Aix-Marseille University, CRN2M, UMR 7286-CNRS, 51, Bd Pierre Dramard, 13344 Marseille, France. t.cuny@chu-nancy.fr
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae
Adolescent
Adult
Dopamine / analogs & derivatives,  metabolism,  pharmacology
Dopamine Agonists / pharmacology*
Ergolines / pharmacology
Female
Genetic Vectors
Humans
Male
Octreotide / pharmacology
Pituitary Neoplasms / drug therapy*,  metabolism,  pathology
Primary Cell Culture
Prolactin / antagonists & inhibitors*,  genetics
Prolactinoma / drug therapy*,  metabolism,  pathology
Receptors, Dopamine D2 / metabolism
Receptors, Somatostatin / genetics,  metabolism*
Somatostatin / analogs & derivatives,  pharmacology
Transfection
Chemical
Reg. No./Substance:
0/BIM 23A760; 0/Dopamine Agonists; 0/Ergolines; 0/Receptors, Dopamine D2; 0/Receptors, Somatostatin; 51110-01-1/Somatostatin; 83150-76-9/Octreotide; 9002-62-4/Prolactin; LL60K9J05T/cabergoline

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


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