PMID- 26671184
OWN - NLM
STAT- MEDLINE
DCOM- 20160711
LR  - 20181202
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 157
IP  - 3
DP  - 2016 Mar
TI  - The Placental Variant of Human Growth Hormone Reduces Maternal Insulin 
      Sensitivity in a Dose-Dependent Manner in C57BL/6J Mice.
PG  - 1175-86
LID - 10.1210/en.2015-1718 [doi]
AB  - 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.
FAU - Liao, Shutan
AU  - Liao S
AD  - 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.
FAU - Vickers, Mark H
AU  - Vickers MH
AD  - 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.
FAU - Stanley, Joanna L
AU  - Stanley JL
AD  - 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.
FAU - Ponnampalam, Anna P
AU  - Ponnampalam AP
AD  - 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.
FAU - Baker, Philip N
AU  - Baker PN
AD  - 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.
FAU - Perry, Jo K
AU  - Perry JK
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151215
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Carrier Proteins)
RN  - 0 (IGFBP5-interacting protein, mouse)
RN  - 0 (Insulin)
RN  - 0 (Placental Hormones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (insulin-like growth factor-1, mouse)
RN  - 12629-01-5 (Human Growth Hormone)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - W06KFL3RDT (somatotropin-binding protein)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - Carrier Proteins/drug effects/genetics/metabolism
MH  - Eating/drug effects
MH  - Female
MH  - Fetal Development/drug effects
MH  - Human Growth Hormone/*pharmacology
MH  - Humans
MH  - Insulin/*metabolism
MH  - *Insulin Resistance
MH  - Insulin-Like Growth Factor I/drug effects/genetics/metabolism
MH  - Liver/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Placental Hormones/*pharmacology
MH  - Pregnancy
MH  - Pregnancy, Animal/*drug effects/metabolism
MH  - RNA, Messenger/drug effects
MH  - Recombinant Proteins/pharmacology
MH  - Trophoblasts/metabolism
EDAT- 2015/12/17 06:00
MHDA- 2016/07/12 06:00
CRDT- 2015/12/17 06:00
PHST- 2015/12/17 06:00 [entrez]
PHST- 2015/12/17 06:00 [pubmed]
PHST- 2016/07/12 06:00 [medline]
AID - 10.1210/en.2015-1718 [doi]
PST - ppublish
SO  - Endocrinology. 2016 Mar;157(3):1175-86. doi: 10.1210/en.2015-1718. Epub 2015 Dec 
      15.