Moleculon endocrinologieal stidies on the rcqulation of synthesis and socretion of hCG( , ) by trophoblastic and non-trophoblastic cells.

滋养细胞和非滋养细胞合成和分泌 hCG( , ) 的分子内分泌学研究。

基本信息

批准号：
61570796
负责人：
MARUO Takeshi
金额：
$ 1.41万
依托单位：
Kobe University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

The regulation of hCG ( , ) mRNA levels and secretion in normal and malignant trophoblasts was investigated by culturing trophoblastic tissues from normal placenta and choriocarcinoma as well as BeWo cells in the presence or absence of steroid hormone, EGF, PDGF, thyroid hormone or dibutyryl cAMP (dbcAMP). Cellular levels of hCG( , ) and hPL mRNAs were quantitatively estimated by mean grain counts on tissue sections hybridized in situ with labeled cDNA probes. Addition of progesterone (5-20 g/ml) to the culture of normal early placenta caused a decrease in the cellular levels of hCG ( , ) mRNAs and a decline in hCG ( , ) secretion, while progesterone did not affect hPL mNAa levels. Addition of 17 -estradiol (1-10 ng/ml) caused an increase in the cellular levels of hCG mRNA together with an increase in hCG secretion without affecting hCG and hPL mRNA levels. In contrast to normal placenta, choriocarcinoma did not respond to the addition of progesterone. This suggests that progesterone selectively suppresses hCG ( , ) synthesis by normal placenta and that the inhibitory regulation of hCG synthesis in choriocarcinoma is different from that in normal placenta.On the other hand, addition of EGF (100ng/ml), PDGF (2 U/ml), L-T_3(10 ^<-8>M) or dbcAMP (1mM) caused significant increases in hCG ( , ) levels in cultures of normal placenta as well as BeWo cell line. This suggests that there are no differences in the stimulatory regulation of hCG synthesis between normal and malignant trophoblasts. However, the magnitude of the stimulatory effects of EGF and DbcAMP on hCG synthesis was much greater in BeWo cells than that in normal trophoblastic tissues. EGF-receptor was localized on syncytiotrophoblast. A tumor promotor, phorbol myristate acetate (PMA), which is a stimulator of protein kinase C, synergistically enhanced cAMP-induced stimulation of hCG synthesis and secretion by BeWo cells.

通过在存在或不存在类固醇激素的情况下，从正常胎盘和绒毛膜和绒毛膜的滋养组织中培养滋养细胞组织，在正常和恶性滋养细胞中的HCG（，）mRNA水平和分泌的调节。通过平均晶粒计数与标记的cDNA探针原位杂交的组织切片对HCG（，）和HPL mRNA的细胞水平进行定量估计。在正常早期胎盘的培养物中添加孕激素（5-20 g/mL）会导致HCG（，）mRNA的细胞水平降低和HCG（，）分泌的下降，而孕酮不影响HPL MNAA水平。添加17-雌二醇（1-10 ng/ml）导致HCG mRNA的细胞水平增加，而HCG分泌的增加而不会影响HCG和HPL mRNA水平。与正常的胎盘相反，绒毛膜癌对孕酮的添加没有反应。 This suggests that progesterone selectively suppresses hCG ( , ) synthesis by normal placenta and that the inhibitory regulation of hCG synthesis in choriocarcinoma is different from that in normal placenta.On the other hand, addition of EGF (100ng/ml), PDGF (2 U/ml), L-T_3(10 ^<-8>M) or dbcAMP (1mM) caused significant increases in正常胎盘培养物以及Bewo细胞系中的HCG（，）水平。这表明正常和恶性滋养细胞之间HCG合成的刺激调节没有差异。然而，在BOWO细胞中，EGF和DBCAMP对HCG合成的刺激作用的大小要比正常滋养细胞组织中的大小要大得多。 EGF受体定位于合成型成素细胞。肿瘤促进源，佛波菌乙酸肉豆蔻酸酯（PMA），它是蛋白激酶C的刺激剂，协同增强了CAMP诱导的刺激HCG对HCG的合成和Bewo细胞分泌。