Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR−/− mice

List, Edward O.; Berryman, Darlene E.; Ikeno, Yuji; Hubbard, Gene B.; Funk, Kevin; Comisford, Ross; Young, Jonathan A.; Stout, Michael B.; Tchkonia, Tamar; Masternak, Michal M.; Bartke, Andrzej; Kirkland, James L.; Miller, Richard A.; Kopchick, John J.

doi:10.18632/aging.100766

Cited by 43 publications

(36 citation statements)

References 52 publications

(78 reference statements)

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“…This difference may be used to explain the differences between these two mouse lines. That is, the changes of growth, body compositions and insulin sensitivities were opposite in these two lines (304,305,306,307,308). Importantly, the MCK males increased maximum lifespan along with decreased inflammation (305,307,308) and they were protected from HF diet-induced metabolic deterioration(306).…”

Section: Muscle-specific Ghrkomentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

Basu

Qian

Kopchick

2018

European Journal of Endocrinology

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Growth hormone (GH) is produced primarily by anterior pituitary somatotroph cells. Numerous acute human (h) GH treatment and long-term follow-up studies and extensive use of animal models of GH action have shaped the body of GH research over the past 40-50 years. Work on the GH receptor (R) knock-out (GHRKO) mice and results of studies on GH resistant Laron Syndrome (LS) patients have helped define many physiological actions of GH including those dealing with metabolism, obesity, cancer, diabetes, cognition, and aging/longevity. In this review, we have discussed several issues dealing with these biological effects of GH and attempt to answer the question of whether decreased GH action may be beneficial.

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Section: Muscle-specific Ghrkomentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

Basu

Qian

Kopchick

2018

European Journal of Endocrinology

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“…In an effort to identify local and systemic effects of GH signaling in its various target organs, several laboratories generated mice with targeted deletion of the GH receptor in the liver, muscle, adipose tissue, pancreatic β-cells or macrophages [43–50]. The resulting animals with organ specific GH resistance were phenotypically very different from the GHRKO mice.…”

Section: Selective Deletion Of the Gh Receptor In Different Gh Targetmentioning

confidence: 99%

“…To determine the role of different organs in mediating the striking effects of global GHR deletion on aging and longevity, the Kopchick laboratory produced new lines of mice with deletion of GHR limited to the adipose tissue, liver or skeletal and cardiac muscles [46, 47, 50]. Growth, body composition, glucose homeostasis and other phenotypic characteristics of animals from each of these lines were unique but none of them reproduced the phenotype of the animals with global GHR deletion (Table 1).…”

Section: Selective Deletion Of the Gh Receptor In Different Gh Targetmentioning

confidence: 99%

“…Moreover, growth and body size after 6 months of age were drastically reduced in mice with liver-specific GHR disruption (LiGHRKO mice) as expected from the suppression of hepatic IGF-1 secretion [51]. Longevity was reduced in FaGHRKO and unaltered in LiGHRKO mice [50, 52]. Normal longevity of LiGHRKO mice most likely represents a net result of the opposing effects of reducing IGF-1 and increasing GH levels.…”

Section: Selective Deletion Of the Gh Receptor In Different Gh Targetmentioning

confidence: 99%

“…Mice with muscle-specific GHR deletion (MuGHRKO) tended to live somewhat longer than controls but this trend was significant only in males from one of the two cohorts used for longevity determination [50]. Apparently, disruption of GH-induced signaling in multiple organs or at a site other than adipose tissue, liver or muscle is required for the remarkable extension of longevity which is consistently observed in both sexes of global GHRKO mice.…”

Section: Selective Deletion Of the Gh Receptor In Different Gh Targetmentioning

confidence: 99%

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The somatotropic axis and aging: Benefits of endocrine defects

Bartke

List

Kopchick

2016

Growth Hormone & IGF Research

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Reduced somatotropic [growth hormone (GH) and insulin-like growth factor-1 (IGF-1)] action has been associated with delayed and slower aging, reduced risk of frailty, reduced age-related disease and functional decline, and with remarkably extended longevity. Recent studies have added to the evidence that these relationships discovered in laboratory populations of mice apply to other mammalian species. However, the relationship of the somatotropic signaling to human aging is less striking, complex and controversial. In mice, targeted deletion of GH receptors (GHR) in the liver, muscle or adipose tissue affected multiple metabolic parameters but failed to reproduce the effects of global GHR deletion on longevity. Continued search for mechanisms of extended longevity in animals with GH deficiency or resistance focused attention on different pathways of mechanistic target of rapamycin (mTOR), energy metabolism, regulation of local IGF-1 levels and resistance to high-fat diet (HFD).

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Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR−/− mice

Cited by 43 publications

References 52 publications

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

The somatotropic axis and aging: Benefits of endocrine defects

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