Endocrine Abstracts

Recently, two new peptides named Orexin-A and Orexin-B, have been implicated in the regulation of feeding behaviour. Studies in starved rats have shown that catabolic activity quickly predominates, reinforced by elevated corticosterone, not driven by ACTH, implicating adrenal activity as a metabolic regulator. In view of these findings, we sought to investigate whether orexin and orexin receptors are present in human fetal and adult adrenals, and therefore may be implicated in...

Prostatic adenocarcinoma (PCa) is the 2nd leading cause of cancer death in US men. Organ-confined PCa can be effectively managed, but there is no durable treatment for advanced disease. Advanced PCa is treated through androgen deprivation therapy, often coupled with direct AR antagonists, as PCa is exquisitely dependent on androgen receptor (AR) activity for survival. Furthermore, recent studies identified AR as a major effector of DNA repair,...

The balance of androgen and estrogen hormone activity determines the degree of breast development in males and females. A predominance of androgen action impedes whereas a predominance of estrogen action promotes breast development. This sex hormone antagonism is mechanistically mediated by androgen and estrogen receptors (AR, ER). The alpha form of ER (ERα) is required for normal breast development and is the driving oncogene in the majority of breast cancers. The AR is ...

A number of different cell types contribute to the cellular architecture of fat tissue. While the fat cell is making important functional contributions to the systemic metabolic well-being, several additional cell types contribute a supportive role to bestow maximal flexibility on the tissue with respect to many biosynthetic and catabolic processes. The adipocyte has morphed into a cell type whose complexity we only start to appreciate. We now understand that: 1) the contribut...

Pancreatic neuroendocrine tumours (PNETs) are increasing in incidence, and have a 5-year survival rate of <50%. This is largely because, despite recent advances, current treatments are often ineffective, and therefore additional therapeutic agents are required. Epigenetic inhibitors may offer a novel class of anti-cancer drugs, as PNETs harbour mutations of chromatin remodelling genes including ATRX and DAXX, while menin, encoded by MEN1, interac...

Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) and Kallmann syndrome (KS) represent two rare phenotypic presentations of humans with hypogonadotropic hypogonadism secondary to GnRH deficiency. KS/nIHH is genetically heterogeneous and is characterized by incomplete penetrance and variable expressivity. Some genetic variants may play the role of modifier alleles or act as ‘second hits’, providing an explanation of this phenotypic variability. In addition to ...

Cardiovascular disease is the major complication of diabetes that drives mortality and morbidity. Individuals with type 2 Diabetes have a 2-fold increased risk of major cardiovascular events (death, myocardial ischemia and stroke). There is also a 2–4-fold increased risk of heart failure, via mechanisms that are partially independent of underlying coronary disease and myocardial ischemia. Diabetes increases cardiovascular disease via multiple mechanisms including accelera...

Many children have been treated for the diagnosis of GH deficiency during childhood. Having reached final height, it was customary to stop the GH therapy. However, even though final height has been achieved, the adolescent ‘child’ is still in the transition phase as far as peak muscle and bone development are concerned. As this transition period is particularly challenging in adolescents that were treated with GH during childhood it is most important to redefine them...

There are robust data from all parts of the World that the incidence of testicular germ cell cancer, which is often associated with dysgenesis and poor spermatogenesis in adjacent ‘normal’ testicular tissue, has been increasing during the past 50 years. There is also evidence of widespread poor semen quality among young men in European countries, where there also have been reports on declining semen quality. Although the latter findings have been subject to controver...

Ablative radioiodine therapy is critical to the treatment of differentiated thyroid cancers and their metastases, and relies on the innate ability of thyroid cells to uptake iodide via the sodium iodide symporter (NIS). As tumours with reduced avidity for radioiodine have a poorer prognosis,it is critical to identify ways to induce NIS activity and hence radioiodine uptake.Pituitary tumor transforming gene (PTTG) and its interacting partner, PTTG-binding...