Coordinate and divergent regulation of corticotropin-releasing factor (CRF) and CRF-binding protein expression in an immortalized amygdalar neuronal cell line
Coordinate and divergent regulation of corticotropin-releasing factor (CRF) and CRF-binding protein expression in an immortalized amygdalar neuronal cell line
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DOI：
10.1210/en.140.1.251
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发表时间：
1999-01-01
期刊：
影响因子：
4.8
通讯作者：
Kasckow, JW
中科院分区：
文献类型：
--
作者：
Mulchahey, JJ;Regmi, A;Kasckow, JW
CRF是一种由41个氨基酸组成的神经肽，以促垂体素作用而闻名。CRF广泛分布于中枢神经系统的下丘脑以外的区域。CRF结合蛋白(CRF-BP)调节CRF的生物利用度，了解CRF-BP的合成调控是理解CRF作用的重要组成部分。为了更好地研究CRF和CRF-BP的调控，将SV40大T抗原导入杏仁核原代培养细胞，使其永生化。筛选出一株表达CRF免疫反应性和信使RNA的克隆株。由该菌株产生的CRF多肽和信息的调节方式与原代培养几乎没有区别。我们还观察到永生化细胞表达CRF-BP免疫反应性和信使RNA。CRF和CRF-BP的表达均受Forsklin和IL-6的正向调节。与CRF不同，佛波醇12-肉豆蔻酸酯-13-乙酸酯或地塞米松可促进CRF-BP信息和多肽的表达。这些结果表明，在该克隆细胞系中CRF和CRF-BP的合成可能受某些药物的平行调节，而不受另一些药物的调节。这些数据还表明，地塞米松可能通过增加CRF-BP的表达而不是通过降低CRF的表达来降低CRF在杏仁核的生物利用度。
CRF is a 41-amino acid neuropeptide best known for its hypophysiotropic actions. CRF is widely distributed in the central nervous system in areas beyond the hypothalamus. CRF-binding protein (CRF-BP) regulates the bioavailability of CRF, and knowledge of the regulation of CRF-BP synthesis is an integral component of understanding the actions of CRF. To better study the regulation of CRF and CRF-BP, primary amygdalar cultures were immortalized by transfection with the SV 40 large T antigen. A clonal line that expresses CRF immunoreactivity and messenger RNA was selected. The production of CRF peptide and message by this line is regulated in a manner indistinguishable from primary cultures. We also observed that the immortalized cells express CRF-BP immunoreactivity and messenger RNA. The expression of both CRF and CRF-BP is positively regulated by forskolin and interleukin-6. Unlike CRF, the expression of CRF-BP message and peptide was increased by phorbol 12-myristate 13-acetate or dexamethasone. These results demonstrate that the synthesis of CRF and CRF-BP in this clonal cell line may be regulated in parallel by some agents but not by others. These data also suggest that dexamethasone may decrease the biological availability of CRF in the amygdala by increasing the expression of CRF-BP, rather than by decreasing CRF expression.