Endocrine Abstracts

Introduction: Long-term repression of the HPA axis is a major side effect of chronic glucocorticoid administration, even after attempted withdrawal of therapy, and complicates management in patients. We have previously shown that the effect of chronic glucocorticoid treatment in vitro is in part mediated by inhibition of expression the POMC transcription factors Neuro D1 and Tpit, and that this is sustained on treatment withdrawal. We have now furth...

Introduction: POMC is activated in ACTH-dependent Cushing’s Syndrome. We have previously shown that RNA interference (RNAi) targeting POMC coding and promoter sequences induces silencing of POMC and a reduction in ACTH. We have modified our most potent exonic sequence with locked nucleic acid (LNA) chemistry. This is purported to increase serum stability. Here we test whether the LNA confers stability without compromising siRNA silencing potency.<...

Introduction: Although current medical therapies for acromegaly are highly effective, 30% of patients are left with inadequately controlled growth hormone (GH) levels. To investigate a novel therapeutic strategy we have used RNA interference (RNAi) to target GH coding and promoter sequences in vitro and assessed the effect on gene expression and DNA methylation.Method: A careful bioinformatics approach revealed only one area in the coding sequence...