PMID- 12933651
OWN - NLM
STAT- MEDLINE
DCOM- 20030916
LR  - 20111117
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 144
IP  - 9
DP  - 2003 Sep
TI  - Deletion, but not antagonism, of the mouse growth hormone receptor results in 
      severely decreased body weights, insulin, and insulin-like growth factor I levels 
      and increased life span.
PG  - 3799-810
AB  - GH participates in growth, metabolism, and cellular differentiation. To study 
      these roles, we previously generated two different dwarf mouse lines, one 
      expressing a GH antagonist (GHA) and the other having a disrupted GH receptor and 
      binding protein gene (GHR -/-). In this study we compared the two dwarf lines in 
      the same genetic background (C57BL/6J). One of the most striking differences 
      between the mouse lines was their weight gain profile after weaning. The weights 
      of the GHA dwarfs gradually approached controls over time, but the weights of the 
      GHR -/- dwarfs remained low throughout the analysis period. Additionally, fasting 
      insulin and glucose levels were reduced in the GHR -/- mice but normal in the GHA 
      mice. IGF-I and IGF binding protein 3 (IGFBP-3) levels were significantly 
      reduced, but by different degrees, in both mouse lines, but IGFBP-1 and -4 levels 
      were reduced and IGFBP-2 levels increased in GHR -/- mice but unaltered in GHA 
      mice. Finally, life span was significantly extended for the GHR -/- mice but 
      remained unchanged for GHA dwarfs. These results suggest that the degree of 
      blockade of GH signaling can lead to dramatically different phenotypes.
FAU - Coschigano, Karen T
AU  - Coschigano KT
AD  - Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA. 
      coschigk@ohio.edu
FAU - Holland, Amy N
AU  - Holland AN
FAU - Riders, Markus E
AU  - Riders ME
FAU - List, Edward O
AU  - List EO
FAU - Flyvbjerg, Allan
AU  - Flyvbjerg A
FAU - Kopchick, John J
AU  - Kopchick JJ
LA  - eng
GR  - AG 19899/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (Insulin-Like Growth Factor Binding Proteins)
RN  - 0 (Receptors, Somatotropin)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9002-72-6 (Growth Hormone)
SB  - IM
MH  - Animals
MH  - Blood Glucose
MH  - Body Weight/physiology
MH  - Cattle
MH  - Dwarfism, Pituitary/blood/genetics/*physiopathology
MH  - Eating/physiology
MH  - Female
MH  - Gene Deletion
MH  - Genotype
MH  - Growth Hormone/antagonists & inhibitors/genetics
MH  - Insulin/*blood
MH  - Insulin-Like Growth Factor Binding Proteins/blood
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Longevity/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Organ Size/physiology
MH  - Receptors, Somatotropin/*genetics
EDAT- 2003/08/23 05:00
MHDA- 2003/09/17 05:00
CRDT- 2003/08/23 05:00
PHST- 2003/08/23 05:00 [pubmed]
PHST- 2003/09/17 05:00 [medline]
PHST- 2003/08/23 05:00 [entrez]
AID - 10.1210/en.2003-0374 [doi]
PST - ppublish
SO  - Endocrinology. 2003 Sep;144(9):3799-810. doi: 10.1210/en.2003-0374.