Somatostatin receptor sst2 gene transfer in human prolactinomas in vitro: Impact on sensitivity to dopamine, somatostatin and dopastatin, in the control of prolactin secretion

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• 作者：Thomas Cuny^a ; ^b ; ^{t.cuny@chu-nancy.fr} ; Amira Mohamed^a ; Thomas Graillon^a ; ^c ; Catherine Roche^a ; Cé ; line Defilles^a ; Anne-Laure Germanetti^d ; Bettina Couderc^e ; Dominique Figarella-Branger^f ; Alain Enjalbert^a ; ^d ; Anne Barlier^a ; ^d ; Alexandru Saveanu^a ; ^d ; ^{alexandru.saveanu@univ-amu.fr} ; ^{alexandru.saveanu@univmed.fr}
• 关键词：Pituitary adenoma ; Prolactinoma ; Dopamine agonist ; Somatostatin receptor ; Dopastatin
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2012
• 期刊代码：109_03037207
• 类别：bio
• 出版时间：15 May, 2012
• 卷：355
• 期：1
• 页码：106-113
• 文件大小：535 K

摘要

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 卤 7.4 vs. 0.1 卤 0.1 copy/copy 尾-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.