Endocrine Abstracts

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: Pro-opiomelanocortin (POMC) is a precursor polypeptide which is cleaved to make adrenocorticotrophic hormone (ACTH) in the anterior pituitary. It is activated in Cushing’s disease. Current therapies for Cushing’s disease are inadequate. RNA interference (RNAi) allows highly specific and effective suppression of gene expression by use of short interfering RNAs (siRNAs).Method: In the current study we employed custom designed siRNAs...

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...

Background: Proopiomelanocortin gene (POMC) and its cleaved product adrenocorticotrophin hormone (ACTH) play an important role in regulation of the hypothalamo-pituitary-adrenal (HPA) axis. ACTH stimulates the adrenal glands to release glucocorticoids. Glucocorticoid has a suppressive effect on ACTH and POMC. This suppression remains long after withdrawal, and may lead to adrenocortical insufficiency. POMC expression is dependent on the activities of some of the positively act...