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

Basu, Reetobrata; Qian, Yanrong; Kopchick, John J.

doi:10.1530/eje-18-0018

Cited by 50 publications

(39 citation statements)

References 329 publications

(223 reference statements)

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“…diabetic nephropathy [56][57][58] , and multi-organ failures leading to a significantly reduced lifespan [59] . Mouse models of GH excess -mice transgenic for bovine GH (bGH) -corroborate the above human data [2,42,[60][61][62] . These pleiotropic effects of GH action positions GH as a truly enigmatic biomolecule and a topic of intense research in human health for the last century.…”

Section: Introductionsupporting

confidence: 54%

“…On the other hand, resistance to cancer has been one of the consistent features of the two cohorts of LS patients in both Israel [34,63,82,83] and Ecuador [33] , with multiple studies focusing on the underlying molecular mechanisms [83][84][85] . Mouse models of dysregulated GH action -the bGH and the GHRKO mice -closely recapitulates the oncogenic profiles of the corresponding human patients [2] . A number of in vivo xenograft studies on bGH, GHRKO, as well as on mice transgenic for a GHR-antagonist (GHA mice) revealed an intrinsic resistance to tumor development and cancer progression due to abrogation of GHR function [2,3,86] .…”

Section: Gh-ghr In Cancermentioning

confidence: 88%

“…A significant volume of research in vitro, in vivo, in clinical specimens and retrospective meta-analysis on human patients of GH-excess (acromegaly) and GH-resistance (LS) have established that a paracrine/ autocrine GH supports oncogenesis and drives neoplasms towards malignancy, metastasis or relapse in multiple tissues [2,3,63] . We refer our readers to a series of relevant reviews by us and colleagues in this regard, compiling the systematic comprehension of the overall and molecular details of how GHR-positive cancer cells exploit the versatile effects of GH action [2][3][4][64][65][66][67][68][69] . In relevance, the association between GH treatment and cancer incidence in GHD patients remains unclear and widely debated [70] .…”

Section: Gh-ghr In Cancermentioning

confidence: 99%

“…On the other hand, the association between cancer risk in human patients of GH-excess/acromegaly has also been unclear. A confounding factor in this case are variations in IGF1normalizing medical interventions (surgery, GHR-inhibitors, somatostatin-analogs) the study participants underwent prior to the study [2] . However, a number of recent large-scale retrospective meta-analyses reveal a distinctly higher standardized incidence ratio for multiple cancers in these patients [52,78] .…”

Section: Gh-ghr In Cancermentioning

confidence: 99%

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The effects of growth hormone on therapy resistance in cancer

Basu

Kopchick

2019

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Pituitary derived and peripherally produced growth hormone (GH) is a crucial mediator of longitudinal growth, organ development, metabolic regulation with tissue specific, sex specific, and age-dependent effects. GH and its cognate receptor (GHR) are expressed in several forms of cancer and have been validated as an anti-cancer target through a large body of in vitro, in vivo and epidemiological analyses. However, the underlying molecular mechanisms of GH action in cancer prognosis and therapeutic response had been sparse until recently. This review assimilates the critical details of GH-GHR mediated therapy resistance across different cancer types, distilling the therapeutic implications based on our current understanding of these effects.

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Section: Introductionsupporting

confidence: 54%

Section: Gh-ghr In Cancermentioning

confidence: 88%

Section: Gh-ghr In Cancermentioning

confidence: 99%

Section: Gh-ghr In Cancermentioning

confidence: 99%

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The effects of growth hormone on therapy resistance in cancer

Basu

Kopchick

2019

CDR

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“…Mice with genetic deficiencies in somatotropic signaling, including the levels (Manini, ) and actions of growth hormone (GH) (Masternak & Bartke, ), have a major longevity advantage over genetically normal (“wild‐type”) animals (Bartke, ). Hypopituitary Ames dwarf (Prop1 df ) mice with deficiency of GH, thyroid‐stimulating hormone (TSH), and prolactin (Bartke & Brown‐Borg, ), and GH receptor knockout (GHRKO) mice with GH resistance (Zhou et al, ), are remarkably long‐lived and exhibit many features of the delayed, healthy aging, and extended longevity (Bartke & Brown‐Borg, ; Basu, Qian, & Kopchick, ). Many phenotypic characteristics shared by these mutants are believed to represent mechanisms of extended longevity.…”

Section: Introductionmentioning

confidence: 99%

Lifespan of long‐lived growth hormone receptor knockout mice was not normalized by housing at 30°C since weaning

et al. 2020

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Growth hormone receptor knockout (GHRKO) mice are remarkably long‐lived and have improved glucose homeostasis along with altered energy metabolism which manifests through decreased respiratory quotient (RQ) and increased oxygen consumption (VO2). Short‐term exposure of these animals to increased environmental temperature (eT) at 30°C can normalize their VO2 and RQ. We hypothesized that increased heat loss in the diminutive GHRKO mice housed at 23°C and the consequent metabolic adjustments to meet the increased energy demand for thermogenesis may promote extension of longevity, and preventing these adjustments by chronic exposure to increased eT will reduce or eliminate their longevity advantage. To test these hypotheses, GHRKO mice were housed at increased eT (30°C) since weaning. Here, we report that contrasting with the effects of short‐term exposure of adult GHRKO mice to 30°C, transferring juvenile GHRKO mice to chronic housing at 30°C did not normalize the examined parameters of energy metabolism and glucose homeostasis. Moreover, despite decreased expression levels of thermogenic genes in brown adipose tissue (BAT) and elevated core body temperature, the lifespan of male GHRKO mice was not reduced, while the lifespan of female GHRKO mice was increased, along with improved glucose homeostasis. The results indicate that GHRKO mice have intrinsic features that help maintain their delayed, healthy aging, and extended longevity at both 23°C and 30°C.

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

Cited by 50 publications

References 329 publications

The effects of growth hormone on therapy resistance in cancer

The effects of growth hormone on therapy resistance in cancer

Lifespan of long‐lived growth hormone receptor knockout mice was not normalized by housing at 30°C since weaning

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