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A New Nonisotopic, Highly Sensitive Assay for the Measurement of Human Placental Growth Hormone: Development and Clinical Implications

Neuroendocrine Unit (Z.W., M.B., S.C.F., C.J.S.) and I. Frauenklinik-Innenstadt (P.B., B.S.), Medizinische Klinik-Innenstadt, Klinikum der Ludwig Maximilians University, 80336 Munich, Germany; and Department of Medicine and Obstetrics/Gynecology, University of Virginia (S.E.K.), Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Christian J. Strasburger, M.D., Medical Clinic, University Hospital Innenstadt, Ludwig Maximilians University, Ziemssenstrasse 1, 80336 Munich, Germany. E-mail: cjs{at}medinn.med.uni-muenchen.de.

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.

This work was supported by a grant from the Dr. Marianne und Fritz Walter Fischer Stiftung im Stifterverband der Deutschen Wissenschaft (to S.C.F.). This work was presented in part at the 83rd Annual Meeting of The Endocrine Society, Denver, Colorado, 2001, p 184 (Abstract P1-162).

Abbreviations: BMI, Body mass index; GW, gestational week; hGH-N, human pituitary GH; hGH-V, human placental GH; hPL, human placental lactogen; IFA, immunofunctional assay; IFMA, immunofluorometric assay; IRMA, immunoradiometric assay; mAb, monoclonal antibody; rhGHBP, recombinant human GH-binding protein.

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