Estrogen actions on lactotroph proliferation are independent of a paracrine interaction with other pituitary cell types: A study using lactotroph-enriched cells
Estrogen actions on lactotroph proliferation are independent of a paracrine interaction with other pituitary cell types: A study using lactotroph-enriched cells
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DOI：
10.1210/en.2006-1484
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发表时间：
2007-07-01
期刊：
影响因子：
4.8
通讯作者：
Arita, Jun
中科院分区：
文献类型：
--
作者：
Ishida, Maho;Takahashi, Wakaba;Arita, Jun
雌激素对雌激素反应组织的促有丝分裂作用被认为是由邻近雌激素受体阳性细胞分泌的旁分泌生长因子介导的。使用垂体催乳素在原代培养，雌激素发挥促有丝分裂和抗有丝分裂的行动，在细胞上下文依赖的方式，我们调查是否旁分泌细胞与其他垂体细胞类型的相互作用是必需的雌激素作用。在垂体细胞中，富集催乳素85%，使用差速沉降上的不连续Percoll梯度，17 β-雌二醇（E2）表现出抗有丝分裂作用的催乳素IGF-I的存在下，这是类似于在控制未富集的细胞。促有丝分裂的行动，也看到在乳营养丰富的细胞时，E2单独给药，与血清相结合，或与腺苷酸环化酶激活剂毛喉素相结合。在通过荧光激活细胞分选从在催乳素启动子控制下表达增强型绿色荧光蛋白的转基因大鼠中收集的90%的乳营养素富集细胞中获得了类似的结果。碱性成纤维细胞生长因子（bFGF）作为旁分泌因子介导雌激素的促有丝分裂作用的假定作用并不被以下结果所支持：1）bFGF抑制乳营养细胞增殖; 2）bFGF的免疫中和作用未能阻断E2诱导的增殖; 3）细胞bFGF水平未被E2处理改变。这些结果表明，抗有丝分裂和促有丝分裂作用的雌激素催乳素不需要旁分泌信号从其他垂体细胞类型和雌激素直接影响催乳素增殖。
The mitogenic action of estrogen on estrogen-responsive tissues is suggested to be mediated by paracrine growth factors secreted from neighboring estrogen receptor-positive cells. Using pituitary lactotrophs in primary culture, on which estrogen exerts both mitogenic and antimitogenic actions in a cell context-dependent manner, we investigated whether a paracrine cell-to-cell interaction with other pituitary cell types was required for estrogen action. In pituitary cells, enriched for lactotrophs by 85% using differential sedimentation on a discontinuous Percoll gradient, 17 beta-estradiol (E2) showed an antimitogenic action on lactotrophs in the presence of IGF-I, which was similar to that in control unenriched cells. Mitogenic actions were also seen in lactotroph-enriched cells when E2 was administered alone, in combination with serum, or in combination with the adenylate cyclase activator forskolin. Similar results were obtained in 90% lactotroph-enriched cells collected by fluorescence-activated cell sorting from transgenic rats expressing enhanced green fluorescent protein under the control of the prolactin promoter. The putative role of basic fibroblast growth factor (bFGF) as a paracrine factor mediating the mitogenic action of estrogen was not supported by the results that: 1) bFGF inhibited lactotroph proliferation; 2) immunoneutralization of bFGF failed to block E2-induced proliferation; and 3) cellular bFGF levels were not altered by E2 treatment. These results suggest that the antimitogenic and mitogenic actions of estrogen on lactotrophs do not require paracrine signals from other pituitary cell types and that estrogen directly influences lactotroph proliferation.