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The Placental Variant of Human Growth Hormone Reduces Maternal Insulin Sensitivity in a Dose-Dependent Manner in C57BL/6J Mice.

journal contribution
posted on 07.03.2016, 12:12 by S. Liao, M. H. Vickers, J. L. Stanley, A. P. Ponnampalam, Philip Newton Baker, J. K. Perry
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.

History

Citation

Endocrinology, 2016, 157 (3), pp. 1175-1186

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY

Version

AM (Accepted Manuscript)

Published in

Endocrinology

Publisher

Endocrine Society

issn

0013-7227

eissn

1945-7170

Acceptance date

09/12/2015

Copyright date

2016

Available date

07/03/2016

Publisher version

http://press.endocrine.org/doi/abs/10.1210/en.2015-1718

Language

en

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