Maternal Growth Hormone Treatment Increases Placental Diffusion Capacity But Not Fetal or Placental Growth in Sheep*

Abstract

We tested the hypothesis that chronic maternal GH administration would increase fetal substrate supply, increase maternal and fetal insulin-like growth factor I (IGF-I) concentrations, and therefore enhance growth in the late gestation fetal sheep. Eleven ewes received bovine GH 0.1 mg/kg twice daily for 10 days, whereas 10 control ewes received saline. GH treatment increased placental capacity for simple diffusion (P Ͻ 0.01), with a trend toward an increase in placental capacity for facilitated diffusion (P ϭ 0.07). GH treatment also lowered maternal and fetal blood urea concentrations, and there was a trend toward increased fetal protein oxidation (P ϭ 0.07). Maternal but not fetal IGF-I and insulin concentrations increased. Fetal and placental growth were not altered by GH treatment. Maternal and fetal metabolic status was significantly affected by maternal food intake. We conclude that maternal GH treatment increases placental transport capacity, but that anabolic effects in the mother may limit fetal substrate supply and therefore prevent an increase in fetal growth. (Endocrinology 138: 5352-5358, 1997) F ETAL GROWTH in late gestation is limited largely by maternal substrate supply and mediated by a number of maternal and fetal hormones. Glucose is the major source of metabolic substrate for the late gestation fetus (1) and is supplied from the mother across the placenta. Birth size is proportional to cord blood insulin-like growth factor 1 (IGF-I) concentrations in a wide range of species (2), and gene deletion studies have shown clearly that fetal IGF-I is critical for fetal growth in late gestation (3-5).Birth size is also related to maternal GH and perhaps IGF-I concentrations (6 -8). GH and placental lactogen (PL) both induce relative insulin resistance in the mother, and thus are postulated to influence fetal growth by increasing maternal glucose levels and hence substrate supply available to the fetus (2). Nevertheless, previous studies of maternal GH administration have produced conflicting results regarding effects on fetal growth (9 -15).We have previously shown in pregnant sheep that shortterm infusion of IGF-I to the mother results in metabolic changes consistent with an increase in substrate uptake from mother to fetus (16), whereas IGF-I infusion to the fetus results in fetal anabolic changes (17). We have therefore speculated that prolonged elevation of IGF-I concentrations on both sides of the placenta would be expected to lead to enhanced fetal growth (16).We would therefore expect that conditions that both increased fetal glucose supply and increased maternal and fetal IGF-I concentrations would be most likely to enhance fetal growth. GH administration to the mother would be expected to increase maternal circulating blood glucose, fatty acid, and IGF-I concentrations. In the fetus, circulating IGF-I concentrations are regulated by fetal blood glucose and insulin concentrations (18 -20). Thus, maternal GH administration, by increasing maternal and hence fetal blood glucose concen...

The Placenta and Intrauterine Programming

“…Another explanation for the increased efficiency of the small placenta is enhanced expression of nutrient transporters per unit surface area. Activity of the placental glucose and amino acid transport systems is influenced by a wide range of environmental factors including heat stress, hypoxia, under‐ and overnutrition as well as exposure to hormones such as glucocorticoids, growth hormone (GH) and leptin (21, 37, 58–61). For example, in the small placenta of the carunclectomised ewe, clearance of 3‐ O ‐methyl glucose, a non‐metabolisable glucose analogue, is increased per kg placenta in late gestation (13).…”

Rising maternal circulating GH during murine pregnancy suggests placental regulation

“…Provided maternal nutrition is adequate, intermittent maternal GH treatment increases foetal growth in non-human species including rats, pigs and sheep (12, 13, 14, 15, 16, 17, 18). Enhanced placental growth and/or function are implicated in these GH-driven increases in foetal growth (14, 15, 16, 17, 18).…”

“…Provided maternal nutrition is adequate, intermittent maternal GH treatment increases foetal growth in non-human species including rats, pigs and sheep (12, 13, 14, 15, 16, 17, 18). Enhanced placental growth and/or function are implicated in these GH-driven increases in foetal growth (14, 15, 16, 17, 18). Although daily exogenous GH administration enhances foetal growth in rats (16, 19, 20, 16), continuous GH administration does not (21), suggesting that GH pattern as well as dose determine its action, as shown by GH-infusion studies in adult male rats (22 23).…”

Placental efficiency and adaptation: endocrine regulation

“…In sheep, short term maternal administration of IGF‐I in late gestation increased placental lactate production by 56% but had little effect on placental blood flow or transfer by simple on facilitated diffusion (Liu et al 1994). When maternal IGF‐I levels were elevated for 10 days by GH treatment in mid to late gestation, there was an increase in the placental capacity for simple diffusion and a trend towards increased placental clearance of MG without a change in placental weight (Harding et al 1997; Jenkinson et al 1999). In contrast, short term administration of IGF‐I directly to fetal sheep reduced placental lactate production by 30% but had no effect on simple diffusion measured as urea clearance (Harding et al 1994).…”