Novel self-regulation of human chorionic gonadotropin biosynthesis in term pregnancy human placenta

Term pregnancy human placenta contains hCG/LH receptor mRNA transcripts and immunoreactive receptor protein. Both the receptor transcripts and receptor proteins are present only in trophoblasts. These findings led us to investigate whether hCG can regulate its own synthesis in term pregnancy human placenta. Treatment of placental tissue in static cultures or in a dynamic superfusion system with increasing concentrations of highly purified hCG provoked a biphasic effect on the steady state hCG subunit mRNA levels. Although low concentrations of hCG (< 200 mIU/ml) were not effective, moderate concentrations (200-1000 mIU/ml) increased, and high concentrations (> or = 5000 mIU/ml) either had no effect or actually decreased mRNA levels relative to the control values. This response was specific, because none of the hCG concentrations tested had any effect on glyceraldehyde-3-phosphate dehydrogenase or beta-actin mRNA levels. The effects of hCG on steady state hCG subunit mRNA levels were paralleled by corresponding changes in tissue hCG protein levels. Endogenous hCG appears to down-regulate alpha-subunit mRNA levels and hCG secretion. The hCG effect is probably receptor mediated, because a receptor antagonist, deglycosylated hCG, partially antagonized the hCG action. Treatment with exogenous hCG also down-regulated its own receptor mRNA and receptor protein levels. hCG regulation of its alpha-subunit and receptor levels involved both transcriptional as well as posttranscriptional mechanisms. In summary, this is the first demonstration of hCG regulating its own synthesis in term pregnancy human placenta. The findings of this study could offer a potential molecular explanation for the profile of hCG levels in normal pregnant women.