Leptin is a circulating hormone that is expressed abundantly and specifically in the adipose tissue1–5. It is involved in the regulation of energy homeostasis, as well as the neuroendocrine and reproductive systems6–11. 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 amount of leptin from the placenta into the maternal circulation as compared with nonpregnant obese women. Leptin production was also detected in a cultured human choriocarcinoma cell line, BeWo cells, and was augmented during the course of forskolin-induced differentiation of cytotrophoblasts into syncytiotro-phoblasts. Plasma leptin levels were markedly 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 physiologic and pathophysiologic significance of leptin in normal pregnancy and gestational trophoblastic neoplasms.
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Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994).
Masuzaki, H. et al. Human obese gene expression: Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes 44, 855–858 (1995).
Ogawa, Y. et al. Molecular cloning of rat obese cDNA and augmented expression in genetically obese Zucker fatty (fa/fa) rats. J. Clin. Invest. 96, 1647–1652 (1995).
Considine, R.V. et al. Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J. Clin. Invest. 95, 2986–2988 (1995).
Frederich, R.C. et al. Expression of ob mRNA and its encoded protein in rodents: impact of nutrition and obesity. J. Clin. Invest. 96, 1658–1663 (1995).
Pelleymounter, M.A. et al. Effects of the obese gene products on body weight regulation in ob/ob mice. Science 269, 540–543 (1995).
Hallas, J.L. et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269, 543–46 (1995).
Campfield, L.A. et al. Recombinant mouse ob protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 269, 546–549 (1995).
Chehab, F.F., Lim, M.E. & Lu, R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nature Genet. 12, 318–320 (1996).
Ahima, R.S. et al. Role of leptin in the neuroendocrine response to fasting. Nature 382, 250–252 (1996).
Chehab, F.F., Mounzih, K., Lu, R. & Lim, M.E. Early onset of reproductive function in normal female mice treated with leptin. Science 275, 88–90 (1997).
Maffei, M. et al. Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA inobese and weight-reducedsubjects. Nature Med. 1, 1155–1161 (1995).
Considine, R.V. et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334, 292–295 (1996).
Hosoda, K. et al. Development of radioimmunoassay for human leptin. Blochem. Biophys. Res. Commun. 221, 234–239 (1996).
Satoh, N. et al. Pathophysiologrc significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats: Evidence for loss of its satiety effect in VMH-lesioned rats. Endocrinology 138, 947–954 (1997).
Burres, N.S. et al. Inhibition of methotrexate-induced differentiation of cultured human choriocarcinoma (BeWo) Cells by thymidine. Cancer Res. 47, 5059–5064 (1987).
Wice, B. et al. Modulation of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Cxp. Cell Res. 186, 306–316 (1990).
Sanfilippo, J.S. & Stoelk, E.M. Endocrinology of the placenta. in The Human Placenta: Clinical Perspectives, (ed. Lavery, J. P.) 179–198 (Aspen, Rockville, 1987).
Frederich, R.C. et al. Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action. Nature Med. 1, 1311–1314 (1995).
Butte, N.F., Hopkinson, J.M. & Nicolson, M.A. Leptin in human reproduction: Serum leptin levels in pregnant and lactating women. J. Clin. Endocrinol. Metab. 82, 585–589 (1997).
Itoh, H. et al. Brain natriuretic peptide is present in the human amniotic fluid and is secreted from amnion cells. J. Clin. Endocrinol. Metab. 76, 907–911 (1993).
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Masuzaki, H., Ogawa, Y., Sagawa, N. et al. Nonadipose tissue production of leptin: Leptin as a novel placenta-derived hormone in humans. Nat Med 3, 1029–1033 (1997). https://doi.org/10.1038/nm0997-1029
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