Suppressors of cytokine signalling and regulation of growth hormone action

Greenhalgh, Christopher J.; Alexander, Warren S.

doi:10.1016/j.ghir.2003.12.011

Cited by 78 publications

(64 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CIS is an effective and specific negative regulator of GH-induced STAT5 activity. It interacts with tyrosine phosphorylated residues on the GHR cytoplasmic tail, thereby masking STAT5 recruitment sites and inhibiting its phosphorylation and activation (Ram & Waxman 2000, Inagaki-Ohara et al 2003, Greenhalgh & Alexander 2004. The significant reduction in the level of CIS in Ames dwarf mice described in the present paper and the dramatic increase previously found for GH-overexpressing mice correlate with the levels of GH displayed by these mice, suggesting a strong regulation of this protein by GH in vivo (Fig.…”

Section: Discussionsupporting

confidence: 71%

“…SOCS-3 seems to be recruited to the GHR-JAK2 complex by binding to tyrosine phosphorylated activated receptor, inhibiting the activity of the associated kinase by preventing substrate access to the catalytic domain. Until now, there is no conclusive evidence of any physiologic role of SOCS-1 and SOCS-3 in growth control (Greenhalgh & Alexander 2004). Although it was demonstrated that SOCS-2 binds to two phosphorylated tyrosines on the GHR, its mechanism of action (Greenhalgh et al 2005), its actions on GH signaling have been disputed, including positive and inhibitory effects on STAT activation in different models (Favre et al 1999, Greenhalgh et al 2002, 2005.…”

Section: Discussionmentioning

confidence: 99%

“…GH induces the expression of CIS and SOCS-1, -2 and -3, apparently via STATs. SOCS proteins are induced by the same pathway they inhibit, therefore acting in a classical negative feedback loop (Greenhalgh & Alexander 2004). The adapter protein SH2-B was described as a potent activator of phosphorylated JAK2, but it was also proposed to bind to the nonphosphorylated kinase, inhibiting its abnormal activation (Rui & Carter-Su 1999.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increased sensitivity to GH in liver of Ames dwarf (Prop1df/Prop1df) mice related to diminished CIS abundance

Miquet

Sotelo²,

Dominici³

et al. 2005

Journal of Endocrinology

View full text Add to dashboard Cite

To investigate the influence of chronic GH deficiency on GH signaling in vivo, we have analyzed Janus kinase (JAK) 2/signal transducers and activators of transcription (STAT) 5 GH signaling pathway, and its regulation by the suppressors of the cytokine signaling SOCS and by the JAK2-interacting protein SH2-B , in liver of Ames dwarf (Prop1 df /Prop1 df ) mice, which are severely deficient in GH, prolactin and TSH, and of their normal littermates. Prop1 df /Prop1 df mice displayed unaltered GH receptor, JAK2 and STAT5a/b protein levels. No significant differences in the basal tyrosine-phosphorylation levels of JAK2 and STAT5a/b were found between both groups of animals. After in vivo administration of a high GH dose (5 µg/g body weight (BW)), the tyrosine-phosphorylation levels of JAK2 and STAT5a/b increased significantly, reaching similar values in normal and dwarf mice.However, after stimulation with lower GH doses (50 and 15 ng/g BW) the tyrosine-phosphorylation level of STAT5a/b was higher in dwarf mice. The protein content of CIS, a SOCS protein that inhibits STAT5 signaling, was approximately 80% lower in dwarf mice liver, while SOCS-2 and SOCS-3 levels were unaltered. The content of SH2-B , a modulator of JAK2 activity, was reduced by approximately 30% in dwarf mice, although this was associated with normal JAK2 response to a high GH dose. In summary, Prop1 df /Prop1 df mice display increased hepatic sensitivity to GH, an effect that could be related to the lower abundance of CIS in this tissue. Furthermore, the lower CIS content found in this model of GH deficiency suggests that CIS protein levels are regulated by GH in vivo.

show abstract

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increased sensitivity to GH in liver of Ames dwarf (Prop1df/Prop1df) mice related to diminished CIS abundance

Miquet

Sotelo²,

Dominici³

et al. 2005

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…The disruption of the immuneprivileged microenvironment is also suggested by the over-expression of ICOSLG gene involved in the activation and regulation of the adaptive immune responses in a number of tissue as well as the pathological testis [21]. On the other hand, our study evidenced an over-expression of SOCS3 that acts as a negative regulator of inflammatory response and its up-regulation suggests the development of protective mechanisms in response to the severe inflammation that seems to affect KS testes [22]. Taken together, these data suggest that deregulation of genes involved in the inflammation process might be responsible of some features of testicular histological findings in KS, especially the high degree of fibrosis that is invariably described as an early event in the testicular involution process of these subjects [7].…”

Section: Gene Modulation Of Inflammatory Response In Ks Testissupporting

confidence: 54%

Deregulation of Sertoli and Leydig cells function in patients with Klinefelter syndrome as evidenced by testis transcriptome analysis

Ferlin¹,

Nicola²,

Garolla³

et al. 2015

EJEA

View full text Add to dashboard Cite

Background: Klinefelter Syndrome (KS) is the most common abnormality of sex chromosomes (47,XXY) and represents the first genetic cause of male infertility. Mechanisms leading to KS testis degeneration are still not completely defined but considered to be mainly the result of germ cells loss. In order to unravel the molecular basis of global testis dysfunction in KS patients, we performed a transcriptome analysis on testis biopsies obtained from 6 azoospermic non-mosaic KS patients and 3 control subjects. Results: The analysis found that, compared to controls, KS patients showed the differential up-and down-expression of 656 and 247 transcripts. The large majority of the deregulated transcripts were expressed by Sertoli cells (SCs) and Leydig cells (LCs). Functional analysis of the deregulated transcripts indicated changes of genes involved in cell death, inflammatory response, lipid metabolism, steroidogenesis, blood-testis-barrier formation and maintenance, as well as spermatogenesis failure.

show abstract

“…There are eight SOCS proteins with conserved structural and functional domains (Greenhalgh & Alexander 2004). They appear to show differential responses to systemic insults (Johnson et al 2001).…”

Section: Growth Hormonementioning

confidence: 99%

Modifying muscle mass – the endocrine perspective

Solomon

Bouloux

2006

Journal of Endocrinology

143

View full text Add to dashboard Cite

This review describes the major hormonal factors that determine the balance between human skeletal muscle anabolism and catabolism in health and disease, with specific reference to age-related muscle loss (sarcopenia). The molecular mechanisms associated with muscle hypertrophy are described, and the central role of the satellite cell highlighted. The biological dynamics of satellite cells, varying between states of quiescence, proliferation and differentiation are strongly influenced by local endocrine factors. The molecular mechanisms of muscle atrophy are examined focussing on the causes of sarcopenia and associations with systemic medical disorders. In addition, evidence is provided that the mechanisms of atrophy and hypertrophy are unlikely to be simple opposites. Novel endocrine mechanisms underpinning mechanotransduction include IGF-I subtypes that may differentiate between endocrine and mechanical signals; their interaction with classical endocrine factors is an active area of translational research. Recently acquired knowledge on the mechanism of anabolic effects of androgens is also reviewed. The increasingly recognised role of myostatin, a negative regulator of muscle function, is described, as well as its potential as a therapeutic target. Strategies to counter age-related sarcopenia thus represent an exciting field of future investigation.

show abstract

Suppressors of cytokine signalling and regulation of growth hormone action

Cited by 78 publications

References 58 publications

Increased sensitivity to GH in liver of Ames dwarf (Prop1df/Prop1df) mice related to diminished CIS abundance

Increased sensitivity to GH in liver of Ames dwarf (Prop1df/Prop1df) mice related to diminished CIS abundance

Deregulation of Sertoli and Leydig cells function in patients with Klinefelter syndrome as evidenced by testis transcriptome analysis

Modifying muscle mass – the endocrine perspective

Contact Info

Product

Resources

About