The primate placenta and human chorionic gonadotropin.

W E Merz
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引用次数: 12

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.

灵长类动物胎盘与人类绒毛膜促性腺激素。
灵长类动物胎盘中合成多种肽类和蛋白质激素,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。它在胎盘中通过妊娠早期的合体血小板细胞表达。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步骤。目前尚不清楚hCG合成是如何在妊娠初期启动和维持的,也不清楚什么控制机制导致了妊娠早期晚期hCG合成的下调。除了一长串其他物质被描述为hCG生物合成的内在胎盘刺激物外,促性腺激素和γ -氨基丁酸似乎起着重要作用。这在某种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全长形式的功能性LH/hCG受体,其长度约为80 kD,表明hCG生物合成的调节原理是自调节。在妊娠早期胎盘以及绒毛膜癌细胞中,似乎存在LH/hCG受体的截断形式(50kd)。在这些情况下,外源性hCG不能下调其自身的合成。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反应。过量的糖基化可能阻止亚基组装。实验性去糖基化诱导不同构象的hCG,部分获得拮抗特性。最近的研究结果表明,cAMP增加了转录和mRNA的稳定性,也扩大了n -糖基化能力,从而可能完成hCG生物合成的整体协调,包括翻译后事件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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