Mechanism of the Stimulatory Effect of Growth Hormone on Longitudinal Bone Growth*

Isaksson, Olle; Lindahl, Anders; Nilsson, Anders; Isgaard, Jörgen

doi:10.1210/edrv-8-4-426

Cited by 561 publications

(252 citation statements)

References 94 publications

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“…Hormones such as growth hormone (GH) can function in both metabolic and immune roles. Growth hormone targets all tissues, although GH stimulates the production of insulin‐like growth factor 1 (IGF‐1) mainly in the liver (Isaksson et al ., 1987). Abnormal high levels of GH can contribute to the induction of insulin resistance (Weaver et al ., 1995), alter inflammatory cytokine levels (Uronen‐Hansson et.…”

Section: Introductionmentioning

confidence: 99%

Long‐lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high‐fat diet on metabolic function and energy expenditure

Hill

Fang

Miquet³

et al. 2016

Aging Cell

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SummaryGrowth hormone (GH) signaling stimulates the production of IGF‐1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high‐fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet‐induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD.

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Section: Introductionmentioning

confidence: 99%

Long‐lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high‐fat diet on metabolic function and energy expenditure

Hill

Fang

Miquet³

et al. 2016

Aging Cell

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“…The actions of GH may in part be mediated by insulinlike growth factor I (IGF-I) according to the dual effector hypothesis of action (Isaksson et al 1987, Daughaday & Rotwein 1989, and/or have a role in a feed-back control of GH secretion as has recently been demonstrated in mice (Sjögren et al 1999). Although IGF-I is expressed locally in many tissues, in mice it has recently been shown that the circulating IGF-I levels are primarily of hepatic origin (Sjögren et al 1999, Yakar et al 1999.…”

Section: Introductionmentioning

confidence: 99%

Growth hormone endocrinology of Atlantic salmon (Salmo salar): pituitary gene expression, hormone storage, secretion and plasma levels during parr-smolt transformation

Ágústsson¹,

Sundell²,

Sakamoto³

et al. 2001

Journal of Endocrinology

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A number of studies on the Atlantic salmon (Salmo salar), have reported changes in plasma GH during parr-smolt transformation, but there is a lack of information about the endocrinology of the GH system during this process. In order to elucidate the mechanisms underlying these changes in plasma GH levels during the parr-smolt transformation of Atlantic salmon, GH mRNA expression in the pituitary was studied together with total pituitary GH content, in vitro GH secretion rate and plasma GH and IGF-I levels. Atlantic salmon were kept in outside tanks, under natural condition from early February until late June. Approximately three times a month fish were killed and pituitaries and blood were sampled for investigation. Further, pituitaries were moved to the laboratory for in vitro GH secretion studies. The results show that the GH system is first activated by an increase in GH secretion rate, which leads to an increase in plasma GH levels and causes a drop in the total GH content of the pituitary. This drop in pituitary GH content is later reversed by an increased GH synthesis seen as an increase in GH mRNA expression. Maximal activation of the GH system is seen to occur in early May, when plasma IGF-I levels reach highest levels, after which a certain deactivation of the GH system takes place. The data show that plasma levels of GH are to a large extent regulated by the secretion rate from the pituitary, although changes in the GH clearance rate are also likely to take place and influence the plasma GH levels. The study further underlines the significant role that the GH-IGF-I axis plays in the parr-smolt transformation of the Atlantic salmon.

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“…In non-hepatic tissues, GH acts on GHR and may stimulate the local production of IGF-I. The hepatic IGF-I was traditionally thought to be the major endocrine factor for postnatal growth (Daughaday & Rotwein 1989) and the local IGF-I was thought to affect tissue growth in a paracrine and/or autocrine manner (Isaksson et al 1987). However, the importance of hepatic IGF-I to animal growth was challenged by a recent report that mice with a liver-specific deletion of the IGF-I gene grow normally despite a dramatic reduction in blood IGF-I (Yakar et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Identification of Sp1 as the transcription factor for the alternative promoter P2 of the bovine growth hormone receptor gene

Jiang¹,

Okamura²,

Boyd³

et al. 2000

Journal of Molecular Endocrinology

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Growth hormone receptor (GHR) mRNA variants that differ in the 5 -untranslated regions (5 -UTR) have been isolated in various species. These 5 -UTR variants are generated from the use of alternative promoters and/or alternative splicing. The 5 -UTR 1B is one of the GHR 5 -UTR variants isolated in the bovine but its homologues are also present in other species. The 5 -UTR 1B is a predominant GHR 5 -UTR expressed in many tissues. In the present study, we screened a bovine genomic library and isolated a 1·7 kb bovine GHR genomic sequence including exon 1B and its 5 flanking region from which the GHR 5 -UTR 1B is generated. Using primer extension, two major transcription start sites were mapped in the bovine exon 1B. Transient transfection analysis of the 5 flanking region of exon 1B confirmed its promoter activity (termed P2) in both Hep G2 and BHK-21 cells. Furthermore, analysis of deletion promoterreporter constructs found that the basal activity of P2 resided in the proximal region of P2. DNase I footprinting analysis and electromobility shift assay (EMSA) identified the ubiquitous transcription factor Sp1 as the binding protein to a GC box-containing DNA element within the proximal P2. Deletion of the GC box greatly reduced the activity of P2 in cell lines. The GC box-containing site also appeared to bind Sp1 in the nuclear extracts from diverse bovine tissues. This suggests that interactions of Sp1 with the GC box-containing element in the proximal region of P2 may be part of the mechanism for the expression of the bovine GHR 5 -UTR 1B in diverse tissues.

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Mechanism of the Stimulatory Effect of Growth Hormone on Longitudinal Bone Growth*

Cited by 561 publications

References 94 publications

Long‐lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high‐fat diet on metabolic function and energy expenditure

Long‐lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high‐fat diet on metabolic function and energy expenditure

Growth hormone endocrinology of Atlantic salmon (Salmo salar): pituitary gene expression, hormone storage, secretion and plasma levels during parr-smolt transformation

Identification of Sp1 as the transcription factor for the alternative promoter P2 of the bovine growth hormone receptor gene

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