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垂体滤泡星状细胞系TtT/GF中功能性促甲状腺激素受体的表达

Functional thyrotropin receptor expression in the pituitary folliculo-stellate cell line TtT/GF.

作者信息

Brokken L J S, Bakker O, Wiersinga W M, Prummel M F

机构信息

Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

Exp Clin Endocrinol Diabetes. 2005 Jan;113(1):13-20. doi: 10.1055/s-2004-830516.

Abstract

Thyrotropin secretion from the anterior pituitary is regulated mainly through TRH and thyroid hormones. Recent findings of a TSH receptor (TSHR) on folliculo-stellate (FS) cells in the human anterior pituitary indicate that TSH secretion might, in addition, be regulated in a paracrine manner via FS cells. In order to elucidate the physiological relevance of TSHR expression in FS cells we evaluated the effects of TSH on a murine FS cell line, TtT/GF. First, Western blot analysis confirmed the expression of TSHR protein in these cells. Second, three potential second messenger pathways were studied. Last, cDNA array hybridization was used to evaluate the effect of TSH on gene expression levels. TSH failed to induce either the adenylate cyclase/cAMP pathway, the phosphatidylinositol/calcium pathway, or the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 pathway. Most of the genes regulated by TSH were related to cell proliferation, cell differentiation, and apoptosis. Moreover, TSH induced STAT5a and TGFbeta2 expression. We report that TtT/GF cells express a functional TSHR that is not coupled to cAMP nor IP (3) but probably signals through the JAK/STAT5a pathway. Functional TSHR expression in this cell line offers an in vitro model to study the role of TSHR in FS cells.

摘要

垂体前叶促甲状腺激素的分泌主要受促甲状腺激素释放激素(TRH)和甲状腺激素调节。近期研究发现,人类垂体前叶的滤泡星状(FS)细胞上存在促甲状腺激素受体(TSHR),这表明促甲状腺激素的分泌可能还通过FS细胞以旁分泌方式进行调节。为了阐明FS细胞中TSHR表达的生理意义,我们评估了促甲状腺激素对小鼠FS细胞系TtT/GF的影响。首先,蛋白质免疫印迹分析证实了这些细胞中TSHR蛋白的表达。其次,研究了三种潜在的第二信使途径。最后,利用cDNA微阵列杂交技术评估促甲状腺激素对基因表达水平的影响。促甲状腺激素未能诱导腺苷酸环化酶/cAMP途径、磷脂酰肌醇/钙途径或Janus激酶(JAK)/信号转导及转录激活因子(STAT)3途径。大多数受促甲状腺激素调节的基因与细胞增殖、细胞分化和细胞凋亡有关。此外,促甲状腺激素诱导了STAT5a和TGFβ2的表达。我们报告称,TtT/GF细胞表达功能性TSHR,该受体不与cAMP或IP(3)偶联,但可能通过JAK/STAT5a途径发出信号。该细胞系中功能性TSHR的表达为研究TSHR在FS细胞中的作用提供了一个体外模型。

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