Nonsteroidal antiestrogen inhibition of protein kinase C in human corpus luteum and placenta.
Nonsteroidal antiestrogen inhibition of protein kinase C in human corpus luteum and placenta.
复制标题
非甾体抗雌激素对人黄体和胎盘中蛋白激酶 C 的抑制作用。
DOI：
10.1016/0006-2952(89)90120-2
复制
发表时间：
1989
影响因子：
5.8
通讯作者：
Clark,MR
中科院分区：
文献类型：
--
作者：
Eyster,KM;Clark,MR
These studies were undertaken to determine whether nonsteroidal antiestrogens would inhibit the calcium/lipid-dependent protein kinase (protein kinase C) activity in hormonally-responsive human reproductive tissues. Cytosol was prepared from human corpus luteum and term placenta. Protein kinase C activity was examined with various antiestrogens, estrogens, and catecholestrogens. The nonsteroidal antiestrogens tamoxifen, clomiphene and Z-4-hydroxytamoxifen inhibited protein kinase C in cytosol from human corpora lutea and placentae in a concentration-dependent manner. Theic50values were 35–45 μM for tamoxifen, 58–66 μM for clomiphene, and 88 μM for hydroxytamoxifen. Protein kinase C purified 600-fold from human placenta was also inhibited by tamoxifen. The estrogens, estradiol and diethylstilbestrol (DES), and the catecholestrogens, 2-hydroxyestradiol and 4-hydroxyestradiol, had no effect on protein kinase C activity, nor were they able to prevent the inhibition of protein kinase C by the antiestrogens. Inhibition of the enzyme by the antiestrogens was competitive with phosphatidylserine and 1,2-diolein. In addition, tamoxifen inhibited enzyme activity stimulated by the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA). The data suggest that the action of these antiestrogens on protein kinase C was a direct inhibition of the enzyme. Furthermore, the site of interaction showed markedly different structural specificity from that of the estrogen receptor,
