期刊
JOURNAL OF ENDOCRINOLOGY
卷 228, 期 3, 页码 R73-R83出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-15-0451
关键词
resistant prolactinomas; dopamine; estradiol; TGF beta 1
资金
- Agencia Nacional de Promocion Cientifica y Tecnica, Buenos Aires, Argentina [PICT 2013-2016 N2136]
- National Institutes of Health [R01 CA034282-25]
Prolactinomas are the most frequently observed pituitary adenomas and most of them respond well to conventional treatment with dopamine agonists (DAs). However, a subset of prolactinomas fails to respond to such therapies and is considered as DA-resistant prolactinomas (DARPs). New therapeutic approaches are necessary for these tumors. Transforming growth factor beta 1 (TGF beta 1) is a known inhibitor of lactotroph cell proliferation and prolactin secretion, and it partly mediates dopamine inhibitory action. TGF beta 1 is secreted to the extracellular matrix as an inactive latent complex, and its bioavailability is tightly regulated by different components of the TGF beta 1 system including latent binding proteins, local activators (thrombospondin-1, matrix metalloproteases, integrins, among others), and TGF beta receptors. Pituitary TGF beta 1 activity and the expression of different components of the TGF beta 1 system are regulated by dopamine and estradiol. Prolactinomas (animal models and humans) present reduced TGF beta 1 activity as well as reduced expression of several components of the TGF beta 1 system. Therefore, restoration of TGF beta 1 inhibitory activity represents a novel therapeutic approach to bypass dopamine action in DARPs. The aim of this review is to summarize the large literature supporting TGF beta 1 important role as a local modulator of pituitary lactotroph function and to provide recent evidence of the restoration of TGF beta 1 activity as an effective treatment in experimental prolactinomas.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据