A new nonisotopic, highly sensitive assay for the measurement of human placental growth hormone: development and clinical implications.
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 microg/liter (GW 7-13) to 2.8 +/- 0.9 microg/liter (GW 18-22), 7.3 +/- 2.6 microg/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.
Wu
Zida
Z
Neuroendocrine Unit, Medizinische Klinik-Innenstadt, Klinikum der Ludwig Maximilians University, 80336 Munich, Germany.
Bidlingmaier
Martin
M
Friess
Stephanie C
SC
Kirk
Susan E
SE
Buchinger
Peter
P
Schiessl
Barbara
B
Strasburger
Christian J
CJ
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001835:Body Weight; D018604:Epitope Mapping; D005260:Female; D005312:Fetal Blood; D005347:Fibroblasts / Q000502:physiology; D015870:Gene Expression; D013006:Growth Hormone / Q000032:analysis* / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008137:Longitudinal Studies; D051379:Mice; D008807:Mice, Inbred BALB C; D010926:Placental Hormones / Q000032:analysis* / Q000276:immunology; D011247:Pregnancy; D011446:Prospective Studies; D011933:Reagent Kits, Diagnostic; D011994:Recombinant Proteins / Q000235:genetics; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; C064980:GH2 protein, human; D020738:Leptin; D010926:Placental Hormones; D011933:Reagent Kits, Diagnostic; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone