The placental variant of human growth hormone reduces maternal insulin sensitivity in a dose-dependent manner in C57BL/6J mice

Liao, Shutan, Vickers, Mark H., Stanley, Joanna L., Ponnampalam, Anna P., Baker, Philip N. and Perry, Jo K. (2016) The placental variant of human growth hormone reduces maternal insulin sensitivity in a dose-dependent manner in C57BL/6J mice. Endocrinology, 157 (3). pp. 1175-1186. ISSN 0013-7227

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Abstract

The human placental GH 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, or 5 mg/kg · d) by osmotic pump from gestational days 12.5 to 18.5. Fetal linear growth was slightly reduced in the 5 mg/kg dose compared with 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 · d significantly increased maternal fasting plasma insulin concentrations with impaired insulin sensitivity observed at day 18.5 as assessed by homeostasis model assessment. At 5 mg/kg · d, 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.

Item Type: Article
Additional Information: Publisher Copyright: © Copyright 2016 by the Endocrine Society.
Uncontrolled Keywords: endocrinology ,/dk/atira/pure/subjectarea/asjc/1300/1310
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 27 Feb 2026 15:30
Last Modified: 27 Feb 2026 15:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/102107
DOI: 10.1210/en.2015-1718

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