Project description:Adipose tissue is a major target of GH action. GH stimulates lipolysis and reduces fat mass. The molecular mechanism underlying cellular and metabolic effects of GH in adipose tissue is not well understood. The aim of this study is to identify GH-responsive genes that regulate lipid metabolism in adipose tissue. Eight men with GH deficiency underwent measurement of plasma free fatty acid (FFA), whole body lipid oxidation and fat biopsies before and after one month of GH treatment (0.5mg/day). Gene expression profiling was performed using Agilent 44K G4112F arrays utilising a two-colour design. Differentially expressed genes were identified using an empirical Bayes, moderate t-test, with a false discovery rate of < 5%. Genes involved in GH receptor signalling, lipolysis, triglyceride biosynthesis, adipocyte differentiation and function were analysed. Target genes were validated by quantitative RT-PCR. GH increased circulating IGF-I and FFA and stimulated fat oxidation. A total of 246 genes were differentially expressed, of which 135 were up-regulated and 111 down-regulated. GH enhanced adipose tissue expression of IGF-I and SOCS3. It did not change expression of key enzymes governing lipolysis, but differentially regulated genes promoting diacylglycerol syntheses. GH repressed hydroxysteroid (11-beta) dehydrogenase 1, which activates local cortisol production, and genes encoding components of extracellular matrix that regulate inflammation. GH induced concordant change in circulating IGF-I and expression in adipose tissue. GH stimulation of lipolysis is mediated at a translational and/or post-translational level. GH suppressed genes encoding local factors regulating adipocyte differentiation, function and inflammation.
Project description:Objective Circulating plasma miRNAs have been increasingly studied in the field of pituitary neuroendocrine tumor (PitNET) research. Our aim was to discover circulating plasma miRNAs species associated with growth hormone (GH) secreting PitNETs and assess how the plasma levels of discovered miRNA candidates are impacted by SSA therapy and whether there is a difference in their levels between GH secreting PitNETs and other PitNET types. Methods miRNA candidates were discovered using the whole miRNA sequencing approach and differential expression analysis. Selected miRNAs were then analyzed using real-time polymerase chain reaction (qPCR). Results Whole miRNA sequencing discovered a total of 19 differentially expressed miRNAs (DEMs) in GH secreting PitNET patients' plasma 24 hours after surgery and 19 DEMs between GH secreting PitNET patients’ plasma and non-functioning (NF) PitNET patients’ plasma. Seven miRNAs were selected for further testing of which miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p showed a significant downregulation in plasma after 1 month of SSA treatment. miR-181a-5p and mir-625-5p were also found to be significantly downregulated in plasma of GH secreting PitNET patients vs. NF PitNET patients. Conclusions Our study suggests that expression of plasma miRNAs miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p in GH secreting PitNETs is affected by SSA treatment. Additionally, miR-625-5p and miR-181a-5p can distinguish GH secreting PitNETs from other PitNET types warranting further research on these miRNAs for treatment efficacy.
Project description:Using an oligonucleotide-based microarray analysis to study the expression of special genes in tbx5 morphants, we demonstrated that GH and some GH-related genes were markedly downregulated.
