Leptin concentrations in maternal serum and amniotic fluid during the second trimenon: differential relation to fetal gender and maternal morphometry

Leptin, a hormone produced by adipocytes, provides information on the availability of fat stores to the hypothalamus and acts as an afferent satiety signal regulating appetite and energy expenditure in both rodents and humans [Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432; Sinha MK. Human leptin: the hormone of adipose tissue. fur J Endocrinol 1997;136:461-4; Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse ob protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995;269:546-9; Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543-6; Saladin R, De Vos P, Guerre-Millo M, Leturque A, Girard J. Staels B, Auwern J. Transient increase in obese gene expression after food intake or insulin administration. Nature 1995;377:527-9; Campfield LA, Smith FJ, Burn P The OB protein (leptin) pathway - a link between adipose tissue mass and central neural networks. Horm Metab Res 1996;28:619-632; Blum WF, Kiess W, Rascher W, editors. Leptin - the voice of the adipose tissue. J&J Edition, JA Earth Verlag, Heidelberg, 1997]. In addition, leptin is thought to play an important role for reproduction and during gestation [Kiess W, Blum WF, Aubert ML. Leptin, puberty and reproductive function: lessons from animal studies and observations in humans. fur J Endocrinol 1997;138:1-4; Barash IA, Cheung CC, Wigle DS, Ren H, Kabitting EB, Kuijer JL, Clifton DK, Steiner RA. Leptin is a metabolic signal to the reproductive system. Endocrinology 1996;133:3144-47; Chehab F, Lim M, Lu R. Correction of the sterility defect in homocygous obese female mice by treatment with the human recombinant leptin. Nature Genetics 1996;12:318-20; Kiess W, Schubring C, Prohaska F, Englaro P, Rascher W, Attanasio A, Blum WF. Leptin in amniotic fluid at term and at midgestation. In: Blum WF, Kiess W, Rascher W, editors. Leptin - the voice of the adipose tissue. J&J Edition, JA Earth Verlag, Heidelberg, 1997]. The purpose of this study was to gain more insight into a putative role of leptin during midgestation. Therefore we have measured leptin concentrations in maternal serum and amniotic fluid using a specific radioimmunoassay (RLA) employing human recombinant leptin for tracer and standard preparation [Blum WF, Kiess W, Rascher W editors, Leptin - The voice of the adipose tissue. J&J Edition, JA Earth Verlag, Heidelberg, 1997; Blum WF, Englaro P, Heiman M, Attanasio Am, Kiess W, Rascher W. Clinical studies of serum leptin. In: Blum WF, Kiess W, Rascher W. Leptin - The voice of the adipose tissue. J&J Edition, JA Earth Verlag, Heidelberg, 1997; Blum WF, Englaro P, Heiman M, Attanasio AM, Kiess W, Rascher W. Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage and testosterone. J Clin Endocrinol Metab 1997;82:2904-2910]. In addition, estriol, hCG and alphafetoprotein were measured in maternal serum. We have asked whether or not leptin concentrations in maternal serum and amniotic fluid were related to maternal BMI and skinfold thickness. Sixty-three healthy pregnant women who were later found to deliver healthy, term children and as a control group 39 healthy non-pregnant women were included in the study. Maternal age was 35 years (median, range 23-46) and gestational age at amniocentesis 14-17 weeks (range). Leptin concentrations in maternal serum at amniocentesis were 3.2-51.9 ng/ml (range) and in amniotic fluid 2.3-30.2 ng/ml (range). Serum leptin levels from non-pregnant women were 2.7-55.4 ng/ml (range). Maternal leptin serum concentrations at the time of amniocentesis correlated significantly with BMI (r=0.54, P<0.001), and with maternal skinfold measurements (iliac r=0.53, P<0.001, subscapular r=0.44, P<0.001; triceps r=0.39, P<0.002 and biceps r=0.41, P<0.001). Similar relations of leptin serum levels and BMI (r=0.53, P=0.001) and skinfold thickness (iliac r=0.65, P<0.001, subscapular r=0.55, P<0.001, triceps r=0.34, P<0.036 and biceps r=0.38, P<0.016) were found in the non-pregnant control group. In contrast, leptin levels in amniotic fluid did not correlate with maternal BMI, skinfold thickness and leptin levels in maternal serum at midgestation. interestingly, the amniotic fluid leptin levels of girls were significantly higher than those of boys (2.6-30.2 ng/ml (range) versus 2.3-15.6 ng/ml (range)). In conclusion high leptin concentrations are found in maternal serum and amniotic fluid at midgestation. Maternal leptin levels and leptin levels in amniotic fluid seem to be derived from different sources. We hypothesize that leptin plays gestation-specific differential roles for the mother and the fetus. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.