The growth hormone–insulin-like growth factor axis in pregnancy

Abstract

The growth hormone (GH)–insulin-like growth factor (IGF) axis is one of the main drivers of mammalian growth and development. Pituitary secretion of GH is pulsatile and under positive and negative hypothalamic control, as well as stimulation from gastric-secreted acyl-ghrelin. GH has anabolic and metabolic effects both directly via the GH-receptor (GHR) and indirectly via stimulation of IGF1 production at multiple target tissues. In this review, we describe the major changes to this axis during pregnancy, with increasing GH abundance in the maternal circulation across multiple species. This stimulates secretion of IGFs, whose bioavailability is also increased by proteolytic cleavage of their circulating binding proteins during pregnancy. These changes in turn induce maternal metabolic adaptations to pregnancy and promote placental function and fetal growth, as does exogenous GH or IGF treatment in animal models of normal and compromised pregnancy. Finally, we explore alternative approaches to enhance maternal GH abundance during pregnancy to promote maternal adaptations, placental function and hence fetal growth.

Ghrelin and the Control of Energy Balance in Females

“…higher in late pregnant mice than in nonpregnant controls but that ghrelin levels were unchanged whereas in mid pregnancy ghrelin levels were lower while total ghrelin levels were unchanged (69). These data suggest that changes in GOAT activity and/or rate of metabolism of acyl ghrelin make important contributions to sex differences in circulating levels of ghrelin.…”

Evolution of Placental Hormones: Implications for Animal Models

“…Fetal growth is regulated by the insulin-like growth factor system with IGF2 as a key factor ( 67 ). IGF2 is expressed in the adults of most amniotes (reptiles, birds and mammals), including human ( 153 ), whereas in mouse and rat Igf2 is expressed in placenta but is largely absent in adults.…”

“…Secretion of placental GH is continuous ( 65 ) whereas pituitary GH is secreted in pulses. Since GH promotes gluconeogenesis, lipolysis and anabolism, it is though that the placental variant increases nutrient availability to the placenta and fetus ( 66 , 67 ). Thus, maternal insulin resistance develops during mid- to late human pregnancy in response to placental GH, thereby ensuring availability of maternal glucose for placental transfer [reviewed in ( 67 )].…”

“…Several IGF binding proteins regulate their availability. For closer consideration the reader is referred to appropriate reviews ( 67 , 70 – 72 ).…”

Symbolic regression analysis of interactions between first trimester maternal serum adipokines in pregnancies which develop pre-eclampsia

“…The “white-box” nature of symbolic regression may enable a much more detailed understanding of the complicated interplay between different endocrine axes, e.g. the GH – IGF axis [58], the IGF system [59], the placenta-brain-axis [60], in pregnancy. This knowledge may in turn aid in defining new therapeutic targets and screening algorithms.…”