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.

在20011年雌二醇（E2）中，使用大鼠乳营养素在原发性培养中使用大鼠乳腺营养刺激了乳酸营养型在原发性培养中的基底增殖，其长潜伏期为96小时，而乳腺营养则抑制了胰岛素诱导的增殖。 E2有丝分裂和抗源作用的ED50分别为85 pm和85 pm。2这种抗源性作用取决于雌激素的活性，而没有观察到雄激素和孕激素的雌激素。3除了有丝分裂作用外，E2抗源性作用除了通过抗雌激素而抑制了Antriped Antried Antriped Andried Antriped Antriped Andried.4除了Indeul.4乳酸营养增生但同时还增加了血清或细胞内环循环AMP水平诱导的增殖而增强的增殖，这表明E2抗源性作用并不依赖于使用脱液细胞中的细胞中的脱孔剂，这并不依赖于E2的抗极源性作用，这并不依赖于脱液的细胞，这在2002年中均不依赖于E2抗源性作用。 IGF-1诱导的增殖和刺激血清诱导的增殖，如乳腺营养中的原代培养物中。然而，E2无法刺激GH_3细胞的基础增殖。2在另一个产生催乳素的细胞系中，GH_4C_1细胞E2抑制IGF-1诱导的增殖，与GH_3细胞不同，与GH_3细胞不同，刺激的基底增殖。3为催乳素和细胞循环蛋白的蛋白质旋转的刺激性刺激性刺激性刺激性刺激蛋白D1 rimunoptive刺激了刺激蛋白D1的刺激性。 E2的有丝分裂和抗源性作用引起的诱导与细胞周期蛋白D1-免疫反应性乳营养素数量的平行变化有关。