The primate placenta and human chorionic gonadotropin.

Abstract

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 gamma-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.