Merz W E
Department of Biochemistry II, University of Heidelberg, Germany.
Exp Clin Endocrinol. 1994;102(3):222-34. doi: 10.1055/s-0029-1211286.
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.
在灵长类动物胎盘中，会合成多种肽类和蛋白质激素，这些激素控制着胎儿的生长发育以及母体与胎儿之间营养物质和代谢产物的交换。在人类中，妊娠早期的维持依赖于生物活性糖蛋白激素人绒毛膜促性腺激素（hCG）的合成。它在妊娠早期由合体滋养层细胞在胎盘中表达。在细胞培养中，hCG的产生似乎标志着细胞滋养层细胞和绒毛膜癌细胞分化过程中的某个特定阶段。目前既不清楚妊娠开始时hCG合成是如何启动和维持的，也不清楚在妊娠早期结束时负责合成下调的控制机制是什么。除了一长串被描述为hCG生物合成内在胎盘刺激物的各种其他物质外，促性腺激素释放激素和γ-氨基丁酸似乎起着重要作用。这在一定程度上建立了与中枢神经系统中促性腺激素合成调节的类比。最近，在足月胎盘中发现了一种约80 kD的全长功能性LH/hCG受体，提示自身调节是hCG生物合成的调节原则。在妊娠早期胎盘以及绒毛膜癌细胞中，似乎存在一种截短形式（50 kd）的LH/hCG受体。在这些情况下，外源性hCG无法下调其自身的合成。hCG的碳水化合物部分影响折叠、亚基组装、循环半衰期、受体相互作用和生物学反应。糖基化过多可能会阻止亚基组装。实验性去糖基化会诱导hCG的不同构象，部分获得拮抗特性。最近的结果表明，增加转录和mRNA稳定性的cAMP也会扩大N-糖基化能力，从而可能实现包括翻译后事件在内的hCG生物合成的全面协调。
