title: The Placental Variant of Human Growth Hormone Reduces Maternal Insulin Sensitivity in a Dose-Dependent Manner in C57BL/6J Mice.
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.
authors.affiliation: Liggins Institute (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), University of Auckland, Auckland 1023, New Zealand; Gravida: National Centre for Growth and Development (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), Auckland 1142, New Zealand; and The First Affiliated Hospital (S.L.), Sun Yat-sen University, 510080 Guangzhou, China.
authors.forename: Shutan
authors.initials: S
authors.lastname: Liao
authors.affiliation: Liggins Institute (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), University of Auckland, Auckland 1023, New Zealand; Gravida: National Centre for Growth and Development (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), Auckland 1142, New Zealand; and The First Affiliated Hospital (S.L.), Sun Yat-sen University, 510080 Guangzhou, China.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Vickers
authors.affiliation: Liggins Institute (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), University of Auckland, Auckland 1023, New Zealand; Gravida: National Centre for Growth and Development (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), Auckland 1142, New Zealand; and The First Affiliated Hospital (S.L.), Sun Yat-sen University, 510080 Guangzhou, China.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Stanley
authors.affiliation: Liggins Institute (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), University of Auckland, Auckland 1023, New Zealand; Gravida: National Centre for Growth and Development (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), Auckland 1142, New Zealand; and The First Affiliated Hospital (S.L.), Sun Yat-sen University, 510080 Guangzhou, China.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Ponnampalam
authors.affiliation: Liggins Institute (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), University of Auckland, Auckland 1023, New Zealand; Gravida: National Centre for Growth and Development (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), Auckland 1142, New Zealand; and The First Affiliated Hospital (S.L.), Sun Yat-sen University, 510080 Guangzhou, China.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Baker
authors.affiliation: Liggins Institute (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), University of Auckland, Auckland 1023, New Zealand; Gravida: National Centre for Growth and Development (S.L., M.H.V., J.L.S., A.P.P., P.N.B., J.K.P.), Auckland 1142, New Zealand; and The First Affiliated Hospital (S.L.), Sun Yat-sen University, 510080 Guangzhou, China.
authors.forename: Jo K
authors.initials: JK
authors.lastname: Perry
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010926:Placental Hormones / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C000607595:IGFBP5-interacting protein, mouse; D007328:Insulin; D010926:Placental Hormones; D012333:RNA, Messenger; D011994:Recombinant Proteins; C519530:insulin-like growth factor-1, mouse; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein