Biosynthesis and secretion of chorionic gonadotropin subunits by organ cultures of first trimester human placenta

The biosynthesis and secretion of human chorionic gonadotropin (hCG) have been studied by pulse-chase labeling techniques in organ cultures of normal first trimester placentae. As we previously reported for human malignant trophoblastic cells (Ruddon et al. (1981) J. Biol. Chem. 256, 5189-5196), first trimester placental tissue produces Mr = 18,000 and 15,000 intracellular forms of alpha subunit and Mr = 24,000 and 18,000 forms of beta subunit. In the placental tissue, there is a greater accumulation of mature subunit forms prior to secretion. The predominant intracellular form of alpha subunit in placental tissue is a high mannose, (Man)8(GlcNAc)2 oligosaccharide-containing form just as it is for malignant trophoblastic cells; however, in placenta there is evidence for a greater content of partially processed intermediates with oligosaccharides smaller than (Man)8(GlcNAc)2. Placental tissue secretes both a large free alpha subunit and an hCG-alpha subunit that is part of complete hCG, but there is a 3- to 6-fold greater secretion (on a molar basis) of free alpha than complete hCG. There is no evidence for the synthesis of high molecular weight prohormone forms that might be precursors to the secreted forms of hCG subunits.