Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

The placental variant of human growth hormone reduces maternal insulin sensitivity in C57BL/6J mice (#19)

Shutan Liao 1 , Mark H Vickers 1 , Joanna L Stanley 1 , Anna Ponnampalam 1 , Phil N Baker 1 , Jo K Perry 1 2
  1. Liggins Institute, University of Auckland, Auckland, New Zealand
  2. University of Auckland, Grafton/ Auckland, AUCKLAND, New Zealand

The human placental growth hormone variant (GH-V) is secreted continuously from the syncytiotrophoblast layer of the placenta during pregnancy, and is thought to play a key role in the maternal adaptation to pregnancy. Maternal GH-V concentrations are closely related to fetal growth in humans. GH-V has also been proposed as a potential candidate to mediate insulin resistance observed later in pregnancy. To determine the effect of maternal GH-V administration on maternal and fetal growth and metabolic outcomes during pregnancy, we examined the dose response relationship for GH-V administration in a mouse model of normal pregnancy. Pregnant C57BL/6J mice were randomized to receive vehicle or GH-V (0.25, 1, 2, 5 mg/kg per day) by osmotic pump from gestational days 12.5-18.5. Fetal linear growth was slightly reduced in the 5 mg/kg dose compared to vehicle and the 0.25 mg/kg groups respectively, whereas placental weight was not affected. GH-V treatment did not affect maternal body weights or food intake. However, treatment with 5 mg/kg per day significantly increased maternal fasting plasma insulin concentrations with impaired insulin sensitivity observed at day 18.5 as assessed by HOMA. At 5 mg/kg per day, there was also an increase in maternal hepatic GH receptor/binding protein (Ghr/Ghbp) and IGF binding protein 3 (Igfbp3) mRNA levels, but GH-V did not alter maternal plasma IGF-1 concentrations or hepatic Igf-1 mRNA expression. Our findings suggest that at higher doses, GH-V treatment can cause hyperinsulinemia and is a likely mediator of the insulin resistance associated with late pregnancy.