Growth Hormone During Development

Osafo, Joy; Wei, Yuhong; Kenth, Gurvinder; Goodyer, Cynthia G.

doi:10.1007/s11154-005-3048-6

Cited by 11 publications

(9 citation statements)

References 77 publications

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“…It is produced by stimulation of many cell factors, which widely exist in all kinds of normal tissues of fetus and adult, especially in hematopoietic organs like the liver and spleen of fetus as well as in tissues with higher metabolism, where expression of SOCS1 is relatively high. 22 Although the physiological functions of SOCS1 have not been fully understood, however, current study has revealed that SOCS1 may have wide and important functions, especially its close correlations with malignant tumors. A primary study found that SOCS1 may protect mouse IL-3-dependent cell line Ba/F3 from etoposide and γ-rays.…”

Section: Discussionmentioning

confidence: 90%

Inhibition of MDR1 in mammary cell carcinoma reverses Multidrug Resistance by SOCS1.

Pradhan¹,

Tripathy²,

Pradhan³

et al. 2016

phcogj

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Introduction: Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. Methods: To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. Results: After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p≤0.01) after RNAi exposure. Moreover, flow cytometry

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Section: Discussionmentioning

confidence: 90%

Inhibition of MDR1 in mammary cell carcinoma reverses Multidrug Resistance by SOCS1.

Pradhan¹,

Tripathy²,

Pradhan³

et al. 2016

phcogj

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“…hGH has major effects on adipose tissue, influencing cell numbers as well as lipid content (3,4,6,20,42,43). In a previous study, we demonstrated that V2 is the predominant hGHR transcript in both preadipocytes and mature adipocytes as well as the major variant expressed as the total hGHR mRNA pool increases during human adipocyte differentiation.…”

mentioning

confidence: 86%

Structure and Activity of the Human Growth Hormone Receptor (hGHR) Gene V2 Promoter

Wei¹,

Puzhko²,

Wabitsch³

et al. 2009

Molecular Endocrinology

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Human GH (hGH) has important effects on growth as well as carbohydrate, fat, and protein metabolism. These actions require the presence of normal levels of a functional hGH receptor (hGHR) on the surface of target cells. hGHR gene expression is characterized by the use of several 5'-noncoding exons and alternative splicing, resulting in the generation of multiple mRNA isoforms. The hGHR V2 transcript is predominant in most tissues, including human fat. However, factors regulating its ubiquitous expression have remained unidentified. The present study was aimed at characterizing the mechanisms regulating hGHR V2 transcription. Two major V2 transcriptional start sites were identified by primer extension assays. The V2 proximal promoter is TATA-less, with several characteristics of a housekeeping gene promoter. Transient transfection analyses of 2.6 kb of the 5'-flanking region of V2 confirmed its promoter activity in multiple primate cell lines. Similar promoter activity patterns were observed in human SGBS preadipocytes and mature adipocytes but with much higher V2 promoter activity in mature adipocytes, suggesting that changes in the availability of specific factors during adipocyte differentiation play a role in V2 promoter regulation. Serial deletion and mutation analyses revealed that transcription of hGHR V2 in different cell types, including adipocytes, is determined by a core promoter and distinct inhibitory and activation domains in the 5'-promoter region as well as within the V2 exon. Our data suggest that V2 transcription is the result of a complex interplay involving multiple factors, to ensure appropriate expression of hGHR in different hGH target cells.

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“…Only a subset of newborns with hGH deficiency or hGHR dysfunction have decreased birth length, suggesting that, while fetal hGH can affect fetal growth, the presence of other fetal growth factors (e.g., insulin, placental lactogen, prolactin) ensures relatively normal intrauterine growth (Gluckman et al 1992, Wit & van Unen 1992, Woods et al 1997, Jensen et al 2005, Mehta et al 2005, Osafo et al 2005.…”

Section: Introductionmentioning

confidence: 99%

Developmental changes in the human GH receptor and its signal transduction pathways

Kenth

Mergelas²,

Goodyer

2008

Journal of Endocrinology

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We previously reported the presence of functional human GH receptors (hGHRs) in the human fetal hepatocyte (FH) as early as the first trimester. Interestingly, fetal serum levels of hGH are in the acromegalic range, yet certain hGH-dependent factors are expressed at very low levels (IGF-I, IGF-binding protein-3), suggesting that fetal liver has limited responsiveness to hGH. To determine whether this is due to the fetal tissue levels of hGHR or factors in the hGH/hGHR axis that might influence hGHR function, we compared hGHR isoforms and downstream signaling proteins in FH versus human adult liver (HAL). Immunoprecipitation/immunoblotting (IB) analyses found similar precursor and mature hGHR forms while RT-PCR assays of truncated (T) hGHR 1-279 , dominant negative for the full-length (FL) receptor, showed similar T/FL mRNA ratios in FH and HAL. IB demonstrated that Janus kinase (JAK) 2, signal transducers and activators of transcription (STAT(1, 3, 5A/B)), and suppressors of cytokine signaling (SOCS(1, 2, 3, cytokineinducible SH2-containing protein (CIS))) proteins were detectable in all FH and HAL tested (12 weeks of fetal age to 60 years); the levels were similar (STAT5B) or lower (JAK2/STAT1/STAT3/STAT5A: 38-53%, SOCS/CIS: 58-76%) in FH compared with HAL. Our studies to date demonstrate that, during hepatocyte development, hGHR levels are lower in the fetal cells but the hGHR isoforms, including the relative amount of truncated versus FL, remain unchanged. The JAK2/STAT/SOCS signaling molecules are present in the FH as early as the first trimester. However, they are generally at !50% level in postnatal liver. These data suggest that low expression of both hGHR and major hGHR signaling components may explain the limited responsiveness of the fetal cells to the high circulating levels of hGH.

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Growth Hormone During Development

Cited by 11 publications

References 77 publications

Inhibition of MDR1 in mammary cell carcinoma reverses Multidrug Resistance by SOCS1.

Inhibition of MDR1 in mammary cell carcinoma reverses Multidrug Resistance by SOCS1.

Structure and Activity of the Human Growth Hormone Receptor (hGHR) Gene V2 Promoter

Developmental changes in the human GH receptor and its signal transduction pathways

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