Endocrine Abstracts

Nuclear receptors control developmental and physiological processes by regulating the transcription of gene networks in specific cells. This is achieved by the recruitment of coactivators and corepressors that lead to chromatin remodelling and alterations in gene transcription. RIP140 is a ligand dependant corepressor for nuclear receptors that plays key roles in adipose tissue and muscle to regulate energy homeostasis.RIP140 regulates carbohydrate and l...

Glucocorticoid (GC) hormone action can be modulated at the pre-receptor level by the endoluminal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). 11βHSD1 is a bidirectional enzyme that primarily acts as an oxo-reductase in vivo, converting the pro-hormone cortisone to its active form cortisol, while its dehydrogenase activity results in inactivation of cortisol to cortisone. 11βHSD1 oxo-reductase activity allows GC reactivation in a tissue s...

BackgroundSR141716 (Rimonabant) has been shown to significantly inhibit food intake and reduce body weight in rodents and humans by antagonising CB1 receptors. The gut hormones peptide YY3–36 (PYY3–36) and oxyntomodulin (OXM), released from L-cells in the small intestine inhibit food intake in both rodents and humans and this effect is thought to be mediated via the hypothalamus.Objective<...

Glucocorticoids (Gcs) are important regulators of cellular homeostasis, with their effects mediated by the intracellular glucocorticoid receptor (GR). Once activated, the GR may initiate rapid effects within the cytoplasm, but also translocate to the nucleus to affect gene transcription. The subcellular localisation of the GR is therefore an important determinant in the cellular response to Gcs.To analyse subcellular trafficking of the GR, HeLa cells wer...

Introduction: The beneficial effect of GH replacement on bone in AGHD patients is mediated by improvements in target organ sensitivity to PTH and phosphocalcium metabolism. In aging women with established osteoporosis, GH and IGF-1 concentrations are lower and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear.Methods: Fourteen postmenopausal women (63.4±2.1 years; mean BMD T score ± ...

Pro-opiomelanocortin (POMC) is endoproteolysed to ACTH and alpha MSH which bind to the melanocortin-1 receptor, (MC-1R), and act as principal mediators of human skin pigmentation. In addition there is increasing evidence that alpha MSH has important anti-inflammatory actions in the skin. The aim of this study was to determine the efficiency of processing and the involvement of the different peptides in melanogenesis. To address this question we utilized specific two-site immun...

Oestrogens are capable of inducing rat prolactin gene transcription through liganded Oestrogen Receptor (ER) binding a degenerate oestrogen response element (ERE) sequence on the promoter 1440 bp upstream of the transcription start site. ER binding is thought to interact with DNA bound Pit-1 leading to chromatin looping bringing enhancer elements into proximity with the transcription start site. This ERE sequence, TGTCActaTGTCA, differs from the consensus GGTCAnnnTGACC by two ...

Glucocorticoids (Gcs) act via the glucocorticoid receptor (GR) to inhibit proliferation of many epithelial cell types, and induce apoptosis in others, notably lymphoblastic leukemia. Resistance to Gcs occurs in human small cell lung cancer (SCLC), manifest clinically as dysregulated secretion of ACTH-related peptides. Currently nothing is known of the biological consequences such resistance causes. We have previously shown that a panel of human SCLC cell lines secrete ACTH rel...

The neuroendocrine and immune systems are closely linked, and cytokines such as IL-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha), secreted by immune cells or neighbouring pituicytes, may have important local effects on pituitary function to modulate endocrine mechanisms of regulation.We have analysed the transcriptional regulation of the human prolactin (hPRL) gene promoter by TNF-alpha. Using stably transfected GH3 cells expressing luciferase und...

IntroductionInsulin-like growth factors-I (IGF-I) and -II (IGF-II) are important in regulation of metabolism and growth. We previously reported in normal weight normoglycaemic individuals that low circulating IGF-II predicts future weight gain. We subsequently investigated whether such relationships persisted in circumstances of abnormal glucose tolerance.MethodIn 224 type 2 diabetes subjects we assessed the ...