P. Licht et al., NOVEL SELF-REGULATION OF HUMAN CHORIONIC-GONADOTROPIN BIOSYNTHESIS INTERM PREGNANCY HUMAN PLACENTA, Endocrinology, 133(6), 1993, pp. 3014-3025
Term pregnancy human placenta contains hCG/LH receptor mRNA transcript
s and immunoreactive receptor protein. Both the receptor transcripts a
nd receptor proteins are present only in trophoblasts. These findings
led us to investigate whether hCG can regulate its own synthesis in te
rm pregnancy human placenta. Treatment of placental tissue in static c
ultures or in a dynamic superfusion system with increasing concentrati
ons of highly purified hCG provoked a biphasic effect on the steady st
ate 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 (greater-than-or-equal-to 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 h
CG 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 probab
ly receptor mediated, because a receptor antagonist, deglycosylated hC
G, 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 off
er a potential molecular explanation for the profile of hCG levels in
normal pregnant women.