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 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.

Kinetics and secretion of placental growth hormone around parturition

“…Birth weight z-scores and BMI were comparable; hence no obvious explanation for the lower PGH levels in early labour was found. In a recent paper, one woman delivering vaginally was observed to have decreasing values of serum PGH shortly before delivery (9), and Wu et al found no explicit decline in PGH values up to 30 min before parturition in two patients (6). The present findings thus resemble these latter observations, as no significant changes in serum PGH values were observed during the course of vaginal delivery.…”

“…It is controversial whether PGH levels decline in the last weeks of pregnancy. In recent studies, no significant decrease was observed (6,8,9); however, the most recent study reported decreasing values from week 37 onwards, which was most pronounced in the group of mothers carrying the smallest fetuses (3). In addition, serum PGH levels have been reported to decline during labour (4,9).…”

Placental Growth Hormone-Related Proteins and Prolactin-Related Proteins

“…Concentrations of IGF-I and hPGH in maternal serum are tightly correlated in the second half of human pregnancy [39]. Therefore, hPGH acts as an agonist of maternal GHRs.…”

Labordiagnostik bei Wachstumshormon-assoziierten Erkrankungen/Biochemical diagnosis of growth hormone related diseases

“…Es unterscheidet sich vom hypophys ä ren GH nur durch wenige Aminos ä uren, so dass es in den meisten GH-Assays kreuzreagiert. Eine spezifi sche Messung des plazentaren Wachstumshormons ist nur mit speziellen Assays m ö glich [5] . Die physiologische Bedeutung dieser plazentaren GH-Sekretion, die bislang nur beim Menschen nachgewiesen wurde, ist unklar.…”