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

通过培养正常胎盘、绒毛膜癌滋养层组织和BeWo细胞，观察在激素、EGF、PDGF、甲状腺激素或二丁酰cAMP(DBcAMP)存在或不存在的情况下，正常和恶性滋养层细胞hCG(，)mRNA水平和分泌的调节。通过与标记的cDNAs原位杂交的组织切片上的平均颗粒计数来定量评估hCG(，)和hPL mRNAs的细胞水平。在正常早期胎盘细胞培养中加入孕酮(5~20g/ml)可引起hCG(，)mRNAs水平下降，hCG(，)分泌减少，而孕酮对hPLmNAa水平无影响。加入17-雌二醇(1-10 ng/ml)后，细胞内hCG mRNA水平升高，hCG分泌增加，但不影响hCG和HPL的mRNA水平。与正常胎盘相比，绒毛膜癌对添加黄体酮没有反应。这表明孕酮选择性地抑制正常胎盘hCG(1)的合成，绒毛膜癌hCG合成的抑制调节与正常胎盘不同。另一方面，加入表皮生长因子(100 ng/ml)、血小板衍生生长因子(2U/ml)、L-T_3(10 mg/L；-8&gt；M)或DBcAMP(1 MM)可使正常胎盘和BeWo细胞株培养的hCG(1)水平显著升高。提示正常滋养层细胞和恶性滋养层细胞对hCG合成的刺激调节没有差异。然而，EGF和DbcAMP对BeWo细胞hCG合成的刺激作用比正常滋养层组织大得多。EGF受体定位于合体滋养层细胞。肿瘤促进剂佛波酯(PMA)是蛋白激酶C的刺激剂，它协同增强cAMP诱导的BeWo细胞hCG合成和分泌的刺激作用。

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.