THE PRIMATE PLACENTA AND HUMAN CHORIONIC-GONADOTROPIN

In the primate placenta various peptide and proteohormones are synthes ized which control growth and development of the fetus as well as the exchange of nutrients and metabolic products between the mother and th e fetus. In humans, maintenance of pregnancy in the first trimester de pends on the synthesis of the bioactive glycoprotein hormone human cho rionic gonadotropin (hCG). It is expressed in placenta by the syncytio throphoblast of early pregnancy. In cell culture, hCG production seems to mark a certain step in the process of differentiation of cytotroph oblasts and choriocarcinoma cells. It is neither understood how hCG sy nthesis 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 v arious other substances which have been described to act as intrinsic placental stimulators of hCG biosynthesis, gonadoliberin and gamma-ami nobutyric acid seem to play an important role. This establishes to som e 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 biosynthesi s. 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. T he carbohydrate moiety of hCG influences folding, subunit assembly, ci rculatory half-life, receptor interaction and biological response. A s urplus of glycosylation may prevent subunit assembly. Experimental deg lycosylation induces a different conformation of hCG, which partly acq uires antagonistic properties. Recent results indicate that cAMP, whic h increases transcription and mRNA stability, also expands the N-glyco sylation capacity and thus may accomplish an over-all coordination of hCG biosynthesis including post-translational events.