Selective inhibition of synthesis and secretion of hCG by progesterone and its correlation with hCG (alpha, beta) mRNA levels

Abstract

In order to elucidate the inhibitory regulation of hCG synthesis, the dynamics of the synthesis and secretion of hCG was investigated by culturing explants of trophoblastic tissues from early placenta and choriocarcinoma in the presence and absence of progesterone, and these results were then compared to those of hPL. The dynamics of mRNAs encoding hCG (alpha, beta) and hPL was assessed by grain counts in the tissue sections hybridized in situ with labelled cDNA probes corresponding to these mRNAs. In the control culture of early placenta, hCG, hCG alpha and hPL in the medium showed marked increases compared to the initial tissue levels, whereas hCG, hCG alpha and immunoreactive hCG beta in the tissue explants remained constant. Progesterone suppressed the secretion of hCG and hCG alpha by placental tissue after 48-hour culture in a dose-response manner and simultaneously decreased the tissue level of immunoreactive hCG beta. However, neither hPL secretion nor hPL tissue level were decreased by progesterone. The in situ hybridization revealed that grain counts for hCG alpha-mRNA and hCG beta-mRNA in the sections prepared from placenta cultured with progesterone were decreased compared to those prepared without progesterone, whereas grain counts for hPL-mRNA remained unchanged. In culture of explants from chorio-carcinoma, no inhibition of synthesis and secretion of hCG by progesterone was found. From these results it will be concluded that progesterone inhibits hCG synthesis through the inhibition of hCG alpha-mRNA and hCG beta-mRNA accumulation and that regulation of hCG synthesis in choriocarcinoma is different from that in the normal placenta.