Does the physiological acromegaly of pregnancy benefit the fetus?

Abstract

Pregnancy is accompanied by notable changes in the secretion of growth hormone (GH) and the insulin-like growth factors (IGFs). A GH variant produced by the placenta is discernible in maternal plasma from early pregnancy, rising exponentially until 37 weeks. Meanwhile, pituitary GH gradually drops to near-undetectable levels. While there might be a modest reduction in circulating IGF-I in early pregnancy, IGF-I increases 2- to 3-fold in the second half, again with a peak at around 37 weeks. Thus, placental GH is believed to replace pituitary GH as the primary stimulus for IGF-I secretion in pregnancy. Several IGF-binding proteins (IGFBPs) including IGFBP-3 are proteolyzed, leading to an elevated free (bioavailable) IGF-I fraction. IGF-II concentrations also appear to show a modest (20-25%) increase in the course of pregnancy. The possible clinical manifestations include edema of face and forearms and carpal tunnel symptoms, reminiscent of the symptoms of acromegaly and the side effects of GH/IGF-I treatment. Neither placental GH nor the maternal IGFs cross the placental barrier, yet evidence from preclinical models is accumulating that they promote trophoblast invasion, placenta growth and maturation, transplacental nutrient transport and, ultimately, fetal growth. The ensemble data strongly suggest that 'gestational acromegaly' develops in order to foster fetoplacental growth.