Transcriptional effect of hypoxia on placental leptin

We observed recently1 that placental leptin is markedly increased in preecl ampsia. Since this disorder is associated with vascular disorders, we have tested the hypothesis that hypoxia regulates leptin expression. We show tha t hypoxia increased leptin mRNA and secretion in trophoblast-derived BeWo c ells. This effect was mediated through leptin promoter activation. 5' delet ion analysis allowed us to delineate two regions containing 1.87 kb and 1.2 0 kb of the promoter which conferred respectively high and low responsivene ss to hypoxia. These data indicate that leptin is up-regulated by hypoxia t hrough a transcriptional mechanism likely to involve distinct hypoxia-respo nsive cis-acting sequences on the promoter. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.