Differential regulation by estrogens of growth and prolactin synthesis in pituitary cells suggests that only a small pool of estrogen receptors is required for growth.
Differential regulation by estrogens of growth and prolactin synthesis in pituitary cells suggests that only a small pool of estrogen receptors is required for growth.
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DOI：
10.1073/pnas.95.5.2325
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发表时间：
1998-03
影响因子：
11.1
通讯作者：
Tae-Yon Chun;David W. Gregg;D. K. Sarkar;Jack Gorski
中科院分区：
文献类型：
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作者：
Tae-Yon Chun;David W. Gregg;D. K. Sarkar;Jack Gorski
PR1细胞是一种分泌催乳素(PRL)的细胞系，来源于在17β-雌二醇处理的Fischer 344大鼠中发现的脑下垂体促乳素肿瘤。我们观察了不同培养条件下雌激素对细胞增殖和催乳素合成的影响。在极低浓度下，雌激素诱导该细胞系的细胞增殖，而抗雌激素则抑制细胞增殖。有趣的是，增殖反应比催乳素反应敏感得多，因为0.01 PM的雌二醇或己烯雌酚可诱导一半最大的生长诱导[大约需要0.1%的雌激素受体(ER)占有率]，而0.01 nM浓度才能诱导一半最大的PRL(约50%的ER占有率)。增殖反应对抗雌激素的敏感性不如PRL反应，因为10 nM浓度的纯抗雌激素ICI182,780不能抑制1 nM雌二醇或己烯雌酚诱导的细胞增殖。相同浓度的ICI182,780使PRL的分泌减少到雌二醇或己烯雌酚诱导的催乳素分泌的1%，这表明ER对增殖的控制和PRL的合成可能是两分法的。在这些细胞中，ER结合的Kd值约为3×10(-11)M。这些在PR1细胞中的结果扩展了以前在其他雌激素调节系统中的研究，表明与特定基因表达的调节相反，细胞增殖只需要少量的ER。他们还提出了这样的问题，即当只有一个配体位置被占据时，或者当雌激素和抗雌激素都占据一个二聚体时，二聚体受体如何发挥作用。
PR1 cells are a prolactin (PRL)-secreting cell line derived from a pituitary lactotroph tumor found in 17beta-estradiol-treated Fischer 344 rats. We examined the effect of estrogen on cell proliferation and PRL synthesis under various culture conditions. Estrogen, at extremely low concentrations, induces cell proliferation in this cell line, whereas antiestrogen inhibits proliferation. Interestingly, the proliferation response is much more sensitive than the PRL response because 0.01 pM estradiol or diethylstilbestrol induces half-maximal growth induction [ approximately 0.1% estrogen receptor (ER) occupancy is required], whereas 0.01 nM concentration is required for half-maximal PRL induction ( approximately 50% ER occupancy is required). The proliferation response is not as sensitive to antiestrogen as the PRL response, because 10 nM concentration of the pure antiestrogen ICI 182,780 could not inhibit 1 nM estradiol- or diethylstilbestrol-induced proliferation. The same concentration of ICI 182,780 decreased PRL secretion to 1% of estradiol- or diethylstilbestrol-induced prolactin secretion suggesting a possible dichotomy of ER control of proliferation and PRL synthesis. The Kd of ER binding in these cells is about 3 x 10(-11) M. These results with the PR1 cells extend previous studies in other estrogen- regulated systems and suggest that only a small pool of ER is required for cell proliferation in contrast with the regulation of expression of specific genes. They also raise questions as to how a dimeric receptor functions when only one ligand site is occupied or when both an estrogen and an antiestrogen occupy one dimer.