Directional secretion and transport of leptin and expression of leptin receptor isoforms in human placental BeWo cells

Placental leptin secretion has important implications for maternal adaptation to pregnancy, fetal growth and development, and local autocrine/paracrine actions within trophoblast. In this study we used a cell culture insert model to examine directional secretion of leptin from the basal and apical surfaces of human choriocarcinoma BeWo cells, and to assess the effects of dexamethasone and syncytialization. Additionally, the effects of dexamethasone on transcellular passage of leptin across BeWo monolayers, and on expression of the leptin receptor isoforms Ob-Rs and Ob-RL were examined. Leptin was secreted into both the basal and apical chambers and was stimulated by dexamethasone. Treatment of BeWo cells with forskolin induced syncytialization and loss of monolayer integrity, but resulted in a marked increase in total leptin secretion, an effect further enhanced by co-treatment with dexamethasone. Bidirectional transfer of I-125-leptin between the apical and basal chambers of BeWo cell cultures was low but indicative of specific transcellular passage of leptin; transfer was unaffected by dexamethasone. Treatment of BeWo cells with forskolin increased Ob-Rs mRNA expression, whilst Ob-RL mRNA expression increased in response to forskolin only in the presence of dexamethasone. In conclusion, our data show that leptin is secreted from both the apical and basal surfaces of BeWo placental cells and is increased by both syncytialization and glucocorticoids. Moreover, transport of exogenous leptin occurred in both the apical to basal and reverse directions, suggesting the potential for maternal-fetal exchange of leptin across the human placenta. (C) 2005 Elsevier Ireland Ltd. All rights reserved.