Expression of the 11β-hydroxysteroid dehydrogenase types 1 and 2 proteins in human and baboon placental syncytiotrophoblast

We have shown that the placenta, via metabolism of maternal cortisol and cortisone by the 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) enzymes types 1 and 2 in the syncytiotrophoblast, regulates the maturation of the fetal pituitary adrenocortical asis 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 11 beta-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 11 beta-HSD-2, it remains to be determined unequivocally whether 11 beta-HSD-1 protein is present in the human placental syncytiotrophoblast To answer this question, enriched fractions of syncytiotrophobrast 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 11 beta-HSD-1. The 11 beta-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 11 beta-HSD-1 to the spncytiotrophoblast was confirmed by immunocytochemistry following antigen retrieval. These results show that both human and baboon placental spncytiotrophoblast expressed the 11 beta-HSD-1, as well as the 11 beta-HSD-2, proteins. Because 11 beta-HSD-1 can function as a reductase, the expression of 11 beta-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. (C) 1999 Harcourt Publishers Ltd.