Nutritional regulation of circulating insulin-like growth factors (IGFs) and their binding proteins in the ovine fetus.

ABSTRACT

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important for fetal and postnatal development, but the regulation of circulating IGFs and IGFBPs has not been as thoroughly investigated in the maternal/fetal unit as in the adult animal where nutrition status plays a regulatory role. We used the chronically-catheterized, late-gestation ovine model and compared circulating IGFs and IGFBPs levels, and hepatic IGF-I mRNA levels. Following a five-day maternal fast, both IGF-I and IGF-II levels were decreased in the maternal and fetal circulation (P < 0.05), accompanied by a decrease in fetal hepatic IGF-I mRNA levels, but the IGFBP2 level was increased and the IGFBP3 level was decreased in maternal circulation, whereas the IGFBP1 level was increased in fetal circulation. In both fed and fasting states, the infusion of glucose (150% of baseline) did not alter IGFs or IGFBPs in either maternal or fetal circulation. To understand the regulation of the endogenous IGF system, rhIGF-I was infused (6.7 nmol/kg fetus/h) into the fetal circulation. While maternal IGFs or IGFBPs remained unchanged, IGF-I infusion into fetal circulation resulted in an increase in IGF-I, a decrease in IGF-II, and an overall increase in the IGFBPs (P < 0.05). Taken together, circulating IGFs and IGFBPs in the ovine fetus are more sensitive to prolonged nutrient deficit than to a brief glucose increase. The nutrition status therefore regulates the IGF system in maternal and fetal circulation which, in turn, may regulate the nutrient utilization for fetal growth.