Our aim was to investigate the effects of one year recombinant human growth hormone (rhGH) therapy on the regulation by insulin of gene expression in muscle and adipose tissue in adults with secondary GH deficiency (GHD). Six GHD subjects without upper-body obesity were submitted to a 3-h euglycemic hyperinsulinemic clamp before and after one year of rhGH therapy. Muscle and abdominal subcutaneous adipose tissue biopsies were taken before and at the end of each clamp. The mRNA levels of insulin receptor, p85 alpha-phosphatidylinositol-3 kinase (p85 alpha PI-3K), insulin dependent glucose transporter (Glut4), hexokinase II, glycogen synthase, lipoprotein lipase (LPL) in muscle and in adipose tissue, hormone sensitive lipase and peroxisome proliferator-activated receptor gamma (PPAR gamma) in adipose tissue were quantified by RT-competitive PCR. One year treatment with rhGH (1.25 IU/day) increased plasma IGF-I concentrations (54+/-7 vs 154+/-11 ng/ml, P<0.01) but did not affect insulin-stimulated glucose disposal rate measured during the hyperinsulinemic clamp (74+/-9 vs 85+/-5 micromol/kg free fat mass/min). Insulin significantly increased p85 alpha PI-3K, hexokinase II and Glut4 mRNA levels in muscle both before and after rhGH treatment. One year of GH therapy increased LPL mRNA levels in muscle (38+/-2 vs 70+/-7 amol/microg total RNA, P<0.05) and in adipose tissue (2490+/-260 vs 4860+/-880 amol/microg total RNA, P<0.05), but did not change the expression of the other mRNAs. We conclude from this study that GH therapy did not alter whole body insulin sensitivity and the response of gene expression to insulin in skeletal muscle of adult GHD patients, but it did increase LPL expression in muscle and adipose tissue. This result could be related to the documented beneficial effect of GH therapy on lipid metabolism.
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Y Khalfallah, G Sassolas, F Borson-Chazot, N Vega, and H Vidal
A D Adamson, D Jackson, and J R E Davis
expression, the vector continues to associate with the chromosomal regions and nuclear matrix but does not integrate. Column 6 – gene knockin or targeted integration. These are stable only approaches and involve targeting either the endogenous gene locus or a
Juan Bernal
the gene is a transcriptional target of T 3 . This will necessarily require the presence of functional TRs in the same cells expressing the gene under regulation, which may not be so in the early periods of embryonic development. General actions of
Min Hu, Yuehui Zhang, Jiaxing Feng, Xue Xu, Jiao Zhang, Wei Zhao, Xiaozhu Guo, Juan Li, Edvin Vestin, Peng Cui, Xin Li, Xiao-ke Wu, Mats Brännström, Linus R Shao, and Håkan Billig
the target genes, resulting in alterations of PGR-targeted gene expression depending on the recruitment of co-regulators ( Patel et al. 2015 ). It has been reported that endometrial PGR expression is elevated in PCOS patients who have anovulation
Praveen Kumar, Vishwa Mohan, Rohit Anthony Sinha, Megha Chagtoo, and Madan M Godbole
, RXR, that bind to thyroid hormone response elements (TREs), which are commonly located in the promoter regions of target genes ( Yen 2001 ). A unique characteristic of TR, unlike many other steroid receptors, is the ability to regulate their target
A L Ferry, D M Locasto, L B Meszaros, J C Bailey, M D Jonsen, K Brodsky, C J Hoon, A Gutierrez-Hartmann, and S E Diamond
domain (TAD). These proteins can have distinct effects on the regulation of target gene expression, tumorigenesis, or the effectiveness of pharmacological approaches to cancer treatment (e.g. c-Jun vs v-Jun ( Jurdic et al. 1995 , Huguier et al. 1998
Chunyan Zhao and Karin Dahlman-Wright
regulation by LXR LXRs activate target genes by binding to DNA sequences associated with target genes. LXRs bind to consensus elements (LXR response elements, LXREs) as heterodimers with isoforms of the retinoid X receptor (RXR), RXRα (NR2B1), RXRβ (NR2B2
Mary C Sugden, Paul W Caton, and Mark J Holness
target genes by transcriptional machinery. In the absence of ligand, PPARα recruits corepressors and histone deacetylases (HDACs), which reverses histone acetylation, resulting in a more compact chromatin environment in which transcription is repressed
W Karges, K Jostarndt, S Maier, A Flemming, M Weitz, A Wissmann, B Feldmann, H Dralle, P Wagner, and BO Boehm
Germ line mutations of the multiple endocrine neoplasia type 1 (MEN1) tumour suppressor gene cause MEN1, a rare familial tumour syndrome associated with parathyroid hyperplasia, adenoma and hyperparathyroidism (HP). Here we investigated the role of the MEN1 gene in isolated sporadic and familial HP. Using RT-PCR single-strand conformational polymorphism screening, somatic (but not germ line) mutations of the MEN1 coding sequence were identified in 6 of 31 (19.3%) adenomas from patients with sporadic primary HP, but none in patients (n=16) with secondary HP due to chronic renal failure. MEN1 mutations were accompanied by a loss of heterozygosity (LOH) for the MEN1 locus on chromosome 11q13 in the adenomas as detected by microsatellite analysis. No DNA sequence divergence within the 5' region of the MEN1 gene, containing the putative MEN1 promoter, was detectable in HP adenomas. Clinical characteristics were not different in HP patients with or without MEN1 mutation. Heterozygous MEN1 gene polymorphisms were identified in 9.6% and 25% of patients with primary and secondary HP respectively. In a large kindred with familial isolated familial HP, MEN1 germ line mutation 249 del4 and LOH was associated with the HP phenotype and a predisposition to non-endocrine malignancies. We suggest that the bi-allelic somatic loss of MEN1 wild-type gene expression is involved in the pathogenesis of a clinically yet undefined subset of sporadic primary HP adenomas. MEN1 genotyping may further help define the familial hyperparathyroidism-MEN1 disease complex, but it seems dispensable in sporadic primary HP.
Richard R Almon, Debra C DuBois, Jin Y Jin, and William J Jusko
, which has many of its effects through post-translational kinase cascades, glucocorticoids have most of their effects by altering transcription of specific genes. These transcriptional effects take two fundamental forms. Many regulated genes contain
