We have shown that the placenta, via metabolism of maternal cortisol and cortisone by the 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes types 1 and 2 in the syncytiotrophoblast, regulates the maturation of the fetal pituitary adrenocortical axis in the baboon. Because the timing and regulation of fetal adrenal development by fetal ACTH in the human seem to parallel that in the baboon, we propose that the placental 11beta-HSD-1 and -2 system also has a role in regulating the development of the fetal pituitary adrenocortical axis during human pregnancy. However, although the human placenta has been shown to express the 11beta-HSD-2, it remains to be determined unequivocally whether 11beta-HSD-1 protein is present in the human placental syncytiotrophoblast. To answer this question, enriched fractions of syncytiotrophoblast were prepared from human and baboon term placentae and proteins probed with polyclonal antibodies directed to amino acids 22-36 or 66-77 of human 11beta-HSD-1. The 11beta-HSD-1 was detected by Western blot analysis as a 32-kDa protein in human and baboon syncytiotrophoblast and as a 34-kDa protein in adult baboon liver. Localization of the 11beta-HSD-1 to the syncytiotrophoblast was confirmed by immunocytochemistry following antigen retrieval. These results show that both human and baboon placental syncytiotrophoblast expressed the 11beta-HSD-1, as well as the 11beta-HSD-2, proteins. Because 11beta-HSD-1 can function as a reductase, the expression of 11beta-HSD-1 in human syncytiotrophoblast would be consistent with the ability of this tissue to convert cortisone to cortisol and provide a means by which transplacental transport of cortisol could regulate the fetal pituitary adrenocortical axis in the human, as recently shown experimentally in the non-human primate baboon model.
Copyright 1999 Harcourt Publishers Ltd.