Requirement for prostaglandin F2 alpha in 17 beta-estradiol stimulation of DNA synthesis in rabbit endometrial cultures.
Requirement for prostaglandin F2 alpha in 17 beta-estradiol stimulation of DNA synthesis in rabbit endometrial cultures.
复制标题
兔子宫内膜培养物中 17β-雌二醇刺激 DNA 合成对前列腺素 F2 α 的需求。
DOI：
10.1002/jcp.1041300216
复制
发表时间：
1987
影响因子：
5.6
通讯作者：
Gerschenson,LE
中科院分区：
文献类型：
--
作者：
Orlicky,DJ;Lieberman,R;Williams,C;Gerschenson,LE
我们推测，两种内源性合成的子宫内膜前列腺素(PGs)--前列腺素F2α(PgF2α)和前列腺素E1(PGE1)在兔子宫内膜的生长控制中起着调节作用。前列腺素F_2α促进脱氧核糖核酸的合成，而前列腺素E_1抑制这种作用。用原代培养的兔子宫内膜细胞研究了这些前列腺素在17-β-雌二醇对DNA合成作用机制中的可能作用。为此，进行了结合实验、第二信使实验和DNA合成实验。17β-雌二醇刺激具有时间依赖性(最佳时间约为6h)，17β-雌二醇浓度依赖(最佳浓度约为10−7m 17β-雌二醇在酚红介质中)增加[~3H]PGF_2α结合量。结合数据的Scatchard类型分析表明，受体数量增加，而与[~3H]PGF_2α的受体亲和力与对照培养相同。这种17β-雌二醇刺激的PgF_2α受体的增加允许次适浓度的PgF_2α(10−9M)增加细胞内肌醇多磷酸的水平，而这个浓度的PgF_2α本身并没有引起细胞内肌醇多磷酸水平的显著变化。在所研究的几种类固醇激素中，17β-雌二醇单独能增加[~3H]PGF_2的α结合。增殖研究表明，在这些原代培养的兔子宫内膜中，17β-雌二醇可以促进DNA的合成，但在吲哚美辛存在的情况下不能，除非在培养液中添加PGF_2α的浓度(10−~9M)接近或高于这些培养物通常积累的浓度。在没有17β-雌二醇刺激的情况下，加入同样低浓度的PGF_2α对DNA合成没有影响。显然，通过对PgF_2α受体的作用，17-β-雌二醇使PgF_2α刺激的DNA合成反应增加了近100倍。17β-雌二醇诱导的DNA合成可被前列腺素E_1抑制，PgF_2α诱导的DNA合成也可被PGE_1抑制。我们认为17β-雌二醇可能通过改变前列环素激动剂：拮抗剂对兔子宫内膜培养的增殖控制来介导其促有丝分裂作用。此外，我们认为，如果17β-雌二醇作为其作用模式的一部分而增加前列腺素F_2α受体，这在同时含有前列腺素和17β-雌二醇受体的其他组织中可能是重要的。
We have hypothesized that two of the endogenously synthsized endometrial prostaglandins (PGs), prostaglandin F2α(PGF2α), and prostaglandin E1(PGE1), play a regulatory role in growth control of the rabbit endometrium. PGF2αincreases DNA synthesis and PGE1inhibits that effect. Primary cultures of rabbit endometrial cells were used to examine the possible role of these PGs in the mechanism of action of 17β‐estradiol on DNA synthesis. Towards this end, binding, second messenger and DNA synthesis experiments were performed. 17β‐estradiol stimulation restulted in a time dependent (optimal: approximately 6 h) and 17β‐estradiol concentration dependent (optimal: approximately 10−7M 17β‐estradiol in phenol red‐containing medium) increase in [3H]PGF2αbinding. Scatchard type analysis of the binding data revealed an increase in receptor number while the receptor affinity for [3H]PGF2αremained the same as in the control treated cultures. This 17β‐estradiol stimulated increase in PGF2αreceptor allowed a suboptimal concentration of PGF2α(10−9M) to increase intracellular levels of inositol polyphosphates, while by itself this concentration of PGF2αcaused no significant change in intracellular inositol polyphosphate levels. 17β‐estradiol, alone among the several studied steroid hormones, could increase [3H]PGF2αbinding. Proliferation studies revealed that, in these primary cultures of rabbit endometrium, 17β‐estradiol could increase DNA synthesis but not in the presence of indomethacin, unless PGF2αwas addd to the medium at a concentration (10−9M) near or above what is normally accumulated in the medium by these cultures. In the absence of 17β‐estradiol stimulation, addition of these same low concentrations of PGF2αhad no effect on DNA synthesis. Apparently, through its effect on the PGF2αreceptor, 17β‐estradiol enhances the PGF2αstimulated DNA synthesis response approximately 100 fold. The DNA synthesis inducd by 17β‐estradiol can be inhibited by PGE1, as can PGF2α‐induced DNA synthesis. We propose that 17β‐estradiol may be mediating its mitogenic effect through an alteration of the prostglandin agonist:antagonist control of proliferation in rabbit endometrial cultures. In additon we suggest that, if 17β‐estradiol acts to increase PGF2αreceptors as part of its mode of action, this may be of importance in other tissues possessing both prostaglandin and 17β‐estradiol receptos.