Key result
Deletion of the growth hormone receptor (GHR -/-), but not GH antagonism (GHA), resulted in persistently low body weights, reduced fasting insulin and glucose, and significantly extended life span.
Why the study?
Does the degree of blockade of GH signaling (deletion vs antagonism) lead to different metabolic and life span phenotypes in mice?
Does the degree of blockade of GH signaling (deletion vs antagonism) lead to different metabolic and life span phenotypes in mice?
Complete deletion of the GH receptor, but not GH antagonism, extends life span and significantly alters metabolic profiles in mice.
Answers are grounded in this paper and cite their sources.
GHR deletion phenotypes in mice should not guide clinical practice; extends models distinguishing receptor deletion from antagonism in aging.
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.
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Coschigano et al. (2003) studied Growth hormone signaling. GHR -/- (deletion of GH receptor) vs. GHA (GH antagonist) and controls was evaluated on Body weight, insulin/glucose levels, IGF levels, and life span. Deletion of the growth hormone receptor (GHR -/-), but not GH antagonism (GHA), resulted in persistently low body weights, reduced fasting insulin and glucose, and significantly extended life span.
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