Endocrine Abstracts

Corticotropin releasing hormone (CRH), and the urocortins (UCN) play key roles in mammalian pathophysiology. Their actions are mediated through two types of G-protein coupled CRH receptors, (R1 and R2) which exhibit distinct pharmacological characteristics and determine specificity of CRH and UCN actions. Several CRH-R1 mRNA splice variants have been identified in native tissues, encoding receptor isoforms with various aminoacid inserts or deletions, termed R1β, R1c, R1d ...

Insulin and the IGFs, the IGFBPs and the insulin and IGF-1 receptors play an important role in cancer progression. Higher levels of circulating total IGF-1 is often associated with an increased risk of developing cancer. Furthermore, the IGF-1 receptor (IGF-1R) is often overexpressed in tumor tissues. This overexpression has been shown to be due to mutations in tumor suppressor genes such as p53, WT1 and BRCA genes. Inhibition of the IGF-1R in culture and preclinical studies l...

There is an increased prevalence of metabolic syndrome in patients with severe GH deficiency. Prior studies used different criteria to define metabolic syndrome but in spite of this limitation, several studies indicate that GH therapy improves many of these parameters. The variable that shows the greatest improvement is waist circumference. Some studies show improvement in both systolic and diastolic blood pressure and in HDL cholesterol. Definitive evidence of decreased level...

Li Fraumeni syndrome (LFS) is a prototypic cancer predisposition syndrome, characterized by multiple, early-onset malignant tumours including breast cancer, bone and soft tissue sarcomas, brain tumors and adrenocortical carcinoma (ACC). LFS is most commonly attributed to germline mutations in the TP53 tumor-suppressor gene. p53 activity is tightly regulated by multiple post-translational mechanisms, disruption of which may lead to tumorigenesis. ACC occurs at disproportionatel...

Brown adipose tissue (BAT) is a thermogenic organ. Its tremendous thermogenic potential is conferred by uncoupling protein 1 (UCP1), which dissociates ATP synthesis from energy substrate oxidation and thereby insures heat production. BAT represents a key thermogenic effector implicated in thermoregulatory thermogenesis. The physiological control of BAT activity and capacity is ensured by the sympathetic nervous system (SNS), which densely innervates brown adipocytes. SNS-media...

Suppression of serum thyrotropin (TSH) is a cornerstone of thyroid cancer treatment, due to the tropic effects of TSH on thyroid cells. However, when deciding on the degree of TSH suppression during initial and long-term management, it is necessary to consider the aggressiveness of the cancer, as well as the potential for adverse effects induced by iatrogenic subclinical or overt hyperthyroidism. More aggressive TSH suppression is indicated in patients with high-risk disease o...

Similar to individual cells, hypothalamic neural circuits profit from intracellular pathways known to work as fuel sensors to maintain energy balance.The mammalian target of rapamycin complex 1 (mTORC1) signaling cascade is among the latest intracellular fuel-sensing pathways to be implicated in the hypothalamic regulation of energy balance.mTORC1 activity is found in both NPY/AgRP- and POMC-producing neurons of the arcuate nucleus...

Contemporary therapies to rationalize the hyperglycaemia in type 2 diabetes mellitus (T2DM) generally involve insulin-dependent mechanisms and lose their effectiveness as pancreatic b-cell function decreases to a greater extent. Kidney emerges out as a novel and potential target to trim down the T2DM. The filtered glucose is reabsorbed principally through the sodium glucose co-transporter-2 (SGLT2), a low affinity transport system, which are present at the luminal surface cell...

Joint stiffness in rheumatoid arthritis (RA) is worse in the morning and has been associated with increased secretion of the pro-inflammatory cytokine IL-6 and in decreased secretion of cortisol, suggesting that clinical symptoms may be related to hormonal and immune circadian variations. We measured 24 h plasma profiles of IL-6 and cortisol in RA patients to determine any changes in IL-6 and cortisol following a two week course of prednisone administered orally in a specially...

G-protein-coupled receptors (GPCRs) constitute the major family of cell surface receptors. They comprise receptors for light, taste and smell as well as ions, small transmitters, peptides and large protein hormones. Given their involvement in fundamental biological processes and their accessibility, GPCRs serve as targets for many classes of drugs, including beta-blockers, antihistamines and opiates.Whereas many biochemical steps involved in GPCR signali...