Expression of the 11β-Hydroxysteroid Dehydrogenase Types 1 and 2 Proteins in Human and Baboon Placental Syncytiotrophoblast

Abstract

We have shown that the placenta, via metabolism of maternal cortisol and cortisone by the 11β-hydroxysteroid dehydrogenase (11β-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 11β-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 11β-HSD-2, it remains to be determined unequivocally whether 11β-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 11β-HSD-1. The 11β-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 11β-HSD-1 to the syncytiotrophoblast was confirmed by immunocytochemistry following antigen retrieval. These results show that both human and baboon placental syncytiotrophoblast expressed the 11β-HSD-1, as well as the 11β-HSD-2, proteins. Because 11β-HSD-1 can function as a reductase, the expression of 11β-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.