NONADIPOSE TISSUE PRODUCTION OF LEPTIN - LEPTIN AS A NOVEL PLACENTA-DERIVED HORMONE IN HUMANS

Leptin is a circulating hormone that is expressed abundantly and speci fically in the adipose tissue(1-5). It is involved in the regulation o f energy homeostasis, as well as the neuroendocrine and reproductive s ystems(6-11). Here, we demonstrate production of leptin by nonadipose tissue, namely, placental trophoblasts and amnion cells from uteri of pregnant women. We show that pregnant women secrete a considerable amo unt of leptin from the placenta into the maternal circulation as compa red with nonpregnant obese women. Leptin production was also detected in a cultured human choriocarcinoma cell line, BeWo cells, and was aug mented during the course of forskolin-induced differentiation of cytot rophoblasts into syncytiotrophoblasts. Plasma leptin levels were marke dly elevated in patients with hydatidiform mole or choriocarcinoma and were reduced after surgical treatment or chemotherapy. Leptin is also produced by primary cultured human amnion cells and is secreted into the amniotic fluid. The present study provides evidence for leptin as a novel placenta-derived hormone in humans and suggests the physiologi c and pathophysiologic significance of leptin in normal pregnancy and gestational trophoblastic neoplasms.