Summary
In the primate placenta various peptide and proteohormones are synthesized which control
growth and development of the fetus as well as the exchange of nutrients and metabolic
products between the mother and the fetus. In humans, maintenance of pregnancy in
the first trimester depends on the synthesis of the bioactive glycoprotein hormone
human chorionic gonadotropin (hCG). It is expressed in placenta by the syncytiothrophoblast
of early pregnancy. In cell culture, hCG production seems to mark a certain step in
the process of differentiation of cytotrophoblasts and choriocarcinoma cells. It is
neither understood how hCG synthesis is initiated and maintained at the beginning
of gestation nor what control mechanisms are responsible for the down-regulation of
the synthesis at the end of the first trimester. Besides a long list of various other
substances which have been described to act as intrinsic placental stimulators of
hCG biosynthesis, gonadoliberin and γ-aminobutyric acid seem to play an important
role. This establishes to some extent an analogy to the regulation of gonadotropin
synthesis in the central nervous system. Recently, a full-length form of functional
LH/hCG receptors of approximately 80 kD has been found in term placenta suggesting
autoregulation as a regulatory principle of hCG biosynthesis. In the first trimester
placenta as well as in choriocarcinoma cells a truncated form (50 kd) of LH/hCG receptors
seems to exist. In these cases, exogenous hCG was unable to down-regulate its own
synthesis. The carbohydrate moiety of hCG influences folding, subunit assembly, circulatory
half-life, receptor interaction and biological response. A surplus of glycosylation
may prevent subunit assembly. Experimental deglycosylation induces a different conformation
of hCG, which partly acquires antagonistic properties. Recent results indicate that
cAMP, which increases transcription and mRNA stability, also expands the N-glycosylation
capacity and thus may accomplish an over-all coordination of hCG biosynthesis including
post-translational events.
Key words
human chorionic gonadotropin - biosynthesis - molecular properties - placenta - cell
differentiation - glycosylation
