Placental growth hormone (GH), GH-binding protein, and insulin-like growthfactor axis in normal, growth-retarded, and diabetic pregnancies: Correlations with fetal growth

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin -dependent diabetes mellitus. GHBP has the potential to modulate the propor tion of free placental GH (PGH) and hence the impact on the maternal GH/ins ulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship a mong glycemia, GHBP, and PGH during pregnancy and to assess the impact of G HBP on the concentration of free PGH. We have extended the analysis of spec imens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding prot ein-1 (IGFBP-1), IGFSP-2, and IGFBP-3 and have related these to maternal ch aracteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free compone nt of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substant ially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gest ation (K36). The mean concentration (+/-SEM) of total PGH increased signifi cantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38) . The mean percentage of free PGH was significantly less in IUGR than in no rmal subjects (67% vs. 79%; P < 0.01). Macrosomia was associated with an in crease in these parameters that did not reach statistical significance. Mul tiple regression analysis revealed that PGH/IGF-I and IGFBP-5 account for 4 0% of the variance in birth weight. IGFBP-3 showed a significant correlatio n with IGF-I, IGF-II, and free and total PGK at K28 and K36. Noninsulin-dep endent diabetes mellitus patients had a lower mean percentage of free PGH ( 65%; P < 0.01), and insulin-dependent diabetics had a higher mean percentag e of free PGH (87%; P < 0.01) than normal subjects. Mean postprandial gluco se at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprand ial and fasting glucose. Although GHBP correlated negatively with PGH (r = -0.52; P <.001), free PGH and total PGH correlated very closely (r = 0.98). The results are consistent with an inhibitory function for GHBP in vivo an d support a critical role for placental GH and IGF-I in driving normal feta l growth.