The amyloid-P precursor protein (APPP) is a ubiquitously expressed adhesion and neuritogenic protein whose processing has previously been shown to be regulated by reproductive hormones including the gonadotropin luteinizing hormone (LH) in human neuroblastoma cells. We report for the first time the expression of APPP in human embryonic stem (hES) cells at the mRNA and protein levels. Using N- and C-terminal antibodies against APPP, we detected both the mature and immature forms of APPP as well as truncated variants (similar to 53 kDa, 47 kDa, and 29 kDa) by immunoblot analyses. Expression of APPP is regulated by both the sternness of the cells and pregnancy-associated hormones. Addition of human chorionic gonadotropin, the fetal equivalent of LH that is dramatically elevated during pregnancy, markedly increased the expression of all APPP forms. These results indicate a critical molecular signaling link between the hormonal environment of pregnancy and the expression of APPP in hES cells that is suggestive of an important function for this protein during early human embryogenesis prior to the formation of neural precursor cells. (C) 2007 Elsevier Inc. All rights reserved.