A new nonisotopic, highly sensitive assay for the measurement of human placental growth hormone: Development and clinical implications

Abstract

Human placental GH (hGH-V) is a variant of pituitary hGH (hGH-N) synthesized and secreted by syncytiotrophoblasts during pregnancy. It differs from hGH-V by only 13 amino acid residues, which makes difficult a specific measurement of hGH-V without interference from hGH-N. To overcome the analytical difficulties, we produced new high affinity monoclonal antibodies specific for hGH-V. Precise screening and epitope mapping allowed identification of a pair of monoclonal antibodies suitable to establish a highly sensitive assay for hGH-V measurement. In a prospective, longitudinal study involving 84 normal pregnancies, we measured maternal concentrations of hGH-V, leptin, IGF-I, and cord blood IGF-I. hGH-V was detectable as early as gestational week (GW) 7. Mean concentrations of hGH-V increased from 0.9 ± 0.5 μg/ liter (GW 7-13) to 2.8 ± 0.9 μg/liter (GW 18-22), 7.3 ± 2.6 μg/liter (GW 28-32), and 13.0 ± 9.6 (GW 37-41). A negative correlation was found between prepregnancy body mass index and hGH-V concentrations from GW 28 onward. Peak hGH-V levels occurred at wk 36.5 ± 2.6 and were significantly lower in obese (P = 0.029) and higher in underweight (P = 0.035) mothers compared with those in mothers of normal weight. The increase in hGH-V between GW 18-22 and GW 28-32 was negatively correlated to the increase in maternal leptin during this period (P = 0.027). Maternal IGF-I concentrations were correlated to those of hGH-V from GW 18 onward (P = 0.039). The strongest correlation was found at GW 28-32 (P = 0.001). Furthermore, maternal hGH-V concentrations in late pregnancy correlated with cord blood IGF-I (P = 0.025) and size of the newborn (P = 0.017). These results, obtained by a new, highly sensitive hGH-V-specific immunoassay, highlight the importance of maternal hGH-V in the regulation of maternal and fetal IGF-I. In addition, the results indicate that maternal weight has a major impact on circulating concentrations of hGH-V.