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Conversion from stimulation to inhibition of the action of estrogen on cell proliferation

雌激素对细胞增殖的作用由刺激转为抑制

基本信息

批准号：
13670058
负责人：
ARITA Jun
金额：
$ 2.3万
依托单位：
University of Yamanashi (Faculty of Medicine)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670058/
关键词：
Estrogen Cell Proliferation Prolactin Anterior Pituitary Gland Insulin Growth Factor

项目摘要

Studies using rat lactotrophs in primary culture in 20011 Estradiol (E2) stimulated basal proliferation of lactotrophs in primary culture with a long latency, 96 h, while it inhibited insulin-induced proliferation within 12 h. The ED50 were 8 and 85 pM for the E2 mitogenic and antimitogenic actions, respectively.2 This antimitogenic action was dependent upon the estrogen activity and not observed for androgens and progestins.3 In addition to the mitogenic action, the E2 antimitogenic action was antagonized by antiestrogens, indicating an estrogen receptor-mediated action.4 E2 inhibited not only insulin-induced lactotroph proliferation but also insulin-like growth factor-1 (IGF-1)-induced proliferation while it enhanced proliferation induced by serum or increased levels of intracellular cyclic AMP, suggesting that the E2 antimitogenic action is not dependent upon proliferative levels but mitogen-specific.Studies using prolactin-producing cell lines in 20021 In GH_3 cells, E2 inhibited IGF-1-induced proliferation and stimulated serum-induced proliferation as in lactotrophs in primary culture. However, E2 failed to stimulate basal proliferation of GH_3 cells.2 In another prolactin-producing cell line, GH_4C_1 cells, E2 inhibited IGF-1-induced proliferation and, unlike to GH_3 cells, stimulated basal proliferation.3 Double immunostaining for prolactin and the cell cycle-regulating protein cyclin D1 revealed that stimulation and inhibition of lactotroph proliferation induced by the mitogenic and antimitogenic actions of E2, respectively, were associated with parallel changes in the number of cyclin D1-immunoreactive lactotrophs.

20011年在原代培养中使用大鼠催乳细胞的研究表明，E2刺激原代培养中催乳细胞的基础增殖，潜伏期较长（96 h），而在12 h内抑制胰岛素诱导的增殖。E2促有丝分裂和抗有丝分裂作用的ED 50分别为8和85 pM。2这种抗有丝分裂作用依赖于雌激素活性，而雄激素和孕激素则未观察到。3除了促有丝分裂作用外，E2的抗有丝分裂作用被抗雌激素拮抗，表明雌激素受体介导的作用。4 E2不仅抑制胰岛素诱导的催乳细胞增殖，而且抑制胰岛素样生长因子-1（IGF-1）。E_2的抗有丝分裂作用不依赖于增殖水平，而依赖于有丝分裂原特异性。E2抑制IGF-1诱导的增殖，并刺激血清诱导的增殖，在原代培养的催乳细胞。在另一种催乳素产生细胞系GH_4C_1中，E2抑制IGF-1诱导的细胞增殖，与GH_3细胞不同，刺激基础增殖。3催乳素和细胞周期的双重免疫染色-细胞周期蛋白D1的调节揭示了促有丝分裂和抗有丝分裂作用诱导的催乳细胞增殖的刺激和抑制，E2分别与细胞周期蛋白D1免疫反应性催乳细胞数量的平行变化相关。