Involvement of cAMP response element-binding protein in the regulation of cell proliferation and the prolactin promoter of lactotrophs in primary culture
Involvement of cAMP response element-binding protein in the regulation of cell proliferation and the prolactin promoter of lactotrophs in primary culture
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DOI：
10.1152/ajpendo.00028.2007
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发表时间：
2007-12-01
影响因子：
5.1
通讯作者：
Arita, Jun
中科院分区：
文献类型：
--
作者：
Ishida, Maho;Mitsui, Tetsuo;Arita, Jun
石田，石井，山川，苏吉山，高桥，志村，远藤，小林，有田，等。cAMP反应元件结合蛋白在乳养菌细胞增殖和催乳素启动子调控中的作用。[J] .中华内分泌杂志，2009,31(2):379 - 379。首次发表于2007年10月9日；doi: 10.1152 / ajpendo.00028.2007。下丘脑激素，包括多巴胺，通过cAMP-protein kinase A （PKA）通路调节垂体细胞的关键功能。pka下游转录因子cAMP反应元件（CRE）结合蛋白（CREB）是一种整合分子，也被许多其他蛋白激酶途径激活。我们研究了CREB在原代细胞培养中参与细胞增殖的调节和PRL启动子对大鼠乳营养细胞的影响。利用重组腺病毒高效地将基因导入垂体细胞。溴隐肽是一种多巴胺能激动剂，已知可降低细胞内cAMP浓度，可抑制PRL启动子活性和乳营养细胞增殖，并伴随CREB介导的转录和CREB磷酸化在乳营养细胞中减少。CREB的显性阴性形式（MCREB）的表达可有效抑制腺苷酸环化酶激活剂forskolin诱导的CREB介导的转录，抑制基础和forskolin诱导的PRL启动子活性和PRL mRNA的表达。MCREB表达降低基础增殖水平，阻断福斯克林诱导的乳养细胞增殖。胰岛素样生长因子I （IGF- I）是乳养动物中一种有效的丝裂原，不影响细胞内cAMP浓度，但会短暂地增加乳养动物CREB的磷酸化。MCREB的表达也抑制了igf -i诱导的嗜乳细胞增殖。这些结果表明，CREB参与正常乳养动物细胞增殖和PRL启动子的调节，多巴胺对这些乳养动物功能的抑制至少部分是由于cAMP-PKA-CREB通路的抑制。
Ishida M, Mitsui T, Yamakawa K, Sugiyama N, Takahashi W, Shimura H, Endo T, Kobayashi T, Arita J. Involvement of cAMP response element-binding protein in the regulation of cell proliferation and the prolactin promoter of lactotrophs in primary culture. Am J Physiol Endocrinol Metab 293: E1529-E1537, 2007. First published October 9, 2007; doi: 10.1152/ajpendo.00028.2007. - Hypothalamic hormones, including dopamine, regulate critical functions of pituitary cells via the cAMP-protein kinase A (PKA) pathway. The PKA-downstream transcription factor cAMP response element (CRE)binding protein ( CREB) is an integrating molecule that is also activated by many other protein kinase pathways. We investigated the involvement of CREB in the regulation of cell proliferation and the PRL promoter of rat lactotrophs in primary cell culture. Recombinant adenoviruses were used for efficient gene delivery into pituitary cells. Bromocriptine, a dopaminergic agonist known to decrease intracellular cAMP concentrations, caused inhibition of PRL promoter activity and lactotroph proliferation, which was accompanied by decreases in CRE-mediated transcription and CREB phosphorylation in lactotrophs. Expression of a dominant-negative form of CREB ( MCREB), which was effective in suppressing CRE-mediated transcription induced by the adenylate cyclase activator forskolin, inhibited basal and forskolininduced PRL promoter activity and PRL mRNA expression. MCREB expression lowered basal proliferative levels and blocked forskolin-induced proliferation of lactotrophs. Insulin-like growth factor I (IGF- I), a potent mitogen in lactotrophs, did not affect intracellular cAMP concentrations but transiently increased lactotroph CREB phosphorylation. MCREB expression also inhibited IGF-I-induced lactotroph proliferation. These results suggest that CREB is involved in the regulation of cell proliferation and the PRL promoter in normal lactotrophs and that dopamine inhibition of these lactotroph functions is at least in part due to inhibition of the cAMP-PKA-CREB pathway.