RAT UTERINE GROWTH AND INDUCTION OF PROGESTERONE-RECEPTOR WITHOUT ESTROGEN-RECEPTOR TRANSLOCATION
RAT UTERINE GROWTH AND INDUCTION OF PROGESTERONE-RECEPTOR WITHOUT ESTROGEN-RECEPTOR TRANSLOCATION
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DOI：
10.1210/endo-116-5-1845
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发表时间：
1985-01-01
期刊：
影响因子：
4.8
通讯作者：
WELSHONS, WV
中科院分区：
文献类型：
--
作者：
JORDAN, VC;TATE, AC;WELSHONS, WV
大鼠子宫对雌二醇（E2）和苯甲酸E2 [E2 B]刺激的反应是孕酮受体产生增加和生长。一系列雌激素（ICI 77，949 [反式-1-（4-羟基苯基）-1，2-二苯基-丁-2-烯]和ICI 47，699 [顺式-1-（对-二甲氨基乙氧基苯基）-1，2-二苯基-2-乙基乙烯]）和抗雌激素三苯乙烯衍生物[他莫昔芬（TAM）、4-羟基-TAM）（4-OH-TAM和4-CH 3-TAM）也不同程度地引起这些反应。这些化合物对雌激素受体（ER）具有一系列亲和力，并能够在体内与子宫中的[3 H]E2竞争结合。在s.c.注射高亲和性配体（E2、E2 B和4-OH-TAM），胞液ER降低。在TAM中也观察到这种降低，TAM在体内代谢为4-OH-TAM。在雌激素反应开始之前的任何时间，用低亲和力化合物（ICI 77，949、ICI 47，699和4-CH 3-TAM）处理的动物的胞质ER没有减少。通过交换试验测定，给予高亲和力配体（E2）后，细胞核ER增加，但给予低亲和力配体（ICI 77，949和4-CH 3-TAM）后，尽管产生了雌激素反应，但未观察到细胞核ER增加。一个功能模型，建议解释ER介导的事件在大鼠子宫，支持最近的建议，即未占用的ER位于核室。在该模型中，大部分未被占据的ER可以在体内驻留在细胞核中;当细胞在体外被破坏时，未被占据的受体或低亲和力配体-ER复合物的解离导致未被占据的受体从细胞核中脱落并被掺入胞质组分中。高亲和力配体-ER复合物保留在细胞核中。ER从细胞质到细胞核的明显移位可能是人为的。这些数据可能反映了未被占据的受体从细胞核的差异提取，而不是受体复合物转移到细胞核。
The rat uterus responds to estradiol (E2) and E2 benzoate [E2B] stimulation with an increase in progesterone receptor production and with growth. These responses were also elicited to varying degrees by a series of estrogenic (ICI 77,949 [trans-1-(4-hydroxyphenyl)-1,2-diphenyl-but-2-ene] and ICI 47,699 [cis-1-(p-dimethylaminoethoxyphenyl)-1,2-diphenyl-2-ethylethylene]) and antiestrogenic triphenylethylene derivatives [tamoxifen (TAM), 4-hydroxy-TAM) (4-OH-TAM and 4-CH3-TAM]. These compounds have a range of affinities for the estrogen receptor (ER) and are able to compete with [3H]E2 binding in the uterus in vivo. Within 1-2 h of a s.c. injection of high affinity ligands (E2, E2B and 4-OH-TAM), there was a decrease in cytosol ER. This decrease was also observed with TAM, which is metabolized to 4-OH-TAM in vivo. There was no decrease in cytosolic ER in animals treated with low affinity compounds (ICI 77,949, ICI 47,699 and 4-CH3-TAM) at any time before the onset of an estrogen response. The nuclear ER increased after administration of a high affinity ligand (E2), as measured by exchange assay, but no increase in nuclear ER was observed after administration of low affinity ligands (ICI 77,949 and 4-CH3-TAM), although estrogenic responses were produced. A functional model was suggested to explain ER-mediated events in the rat uterus that supports the recent proposal that unoccupied ER is located in the nuclear compartment. In this model, the majority of unoccupied ER may reside in the nucleus in vivo; when the cells are disrupted in vitro, the unoccupied receptor or dissociation of low affinity ligand-ER complex causes unoccupied receptor to fall out of the nucleus and to be incorporated into the cytosolic fraction. The high affinity ligand-ER complexes are retained in the nucleus. The apparent translocation of the ER from the cytoplasm to the nucleus may be an artifact. The data may reflect differential extraction of unoccupied receptors from the nucleus rather than transfer of receptor complexes to the nucleus.