Endocrine Abstracts

The endoplasmic reticulum (ER) is a metabolic compartment participating in virtually all anabolic and catabolic branches of cellular metabolism. The redox balance of pyridine nucleotides is a major regulator of the metabolism. Several observations demonstrate their presence in the lumen of the ER. NADPH donates electrons for biosynthetic reactions, biotransformation and antioxidant defense; its reduced state is ensured by NADP+-dependent dehydrogenases. In the ER lu...

I first developed a research interest in the adrenal cortex about 50 years ago. As for many others, these studies gave a detailed insight into several important, though necessarily focused aspects. Teaching endocrinology to undergraduates, it was easy to explain the functions of the gland by following the usual well-trodden paths. Over several years, however, I have come to realize that, despite all that, I still don’t actually know what the adrenal cortex is for. ...

The Thyroid Epidemiology and Audit Research Study (TEARS) involves electronic linkage of various clinical datasets to establish a comprehensive thyroid dataset (“TEARS database”). This includes linking a thyroid follow-up register, all regional biochemistry results, regional prescribing data, a radioactive iodine database, hospital admissions and the General Register of Deaths, all of which use a common patient identification number. Specific algorithms were used to ...

Preservation of a functional pancreatic beta cell mass is essential for normal blood glucose homeostasis. The molecular mechanisms through which beta cells sense changes in blood glucose concentration and decode these as enhanced insulin release will be discussed. I shall describe evidence that AMP-activated protein kinase is a key part of this machinery, implicated both in the acute regulation of insulin and in the regulation of beta cell apoptosis. I shall also discuss the h...

A variety of rapid responses to steroid hormones have been identified during the last decade. In contrast to classical actions mediated via nuclear receptors with a time lag of hours, rapid actions occur within seconds or minutes via second messenger signalling cascades. Classical genomic actions are well-defined and sensitive to transcription and protein synthesis inhibitors. Steroid hormones enter the cell by diffusion or via transport proteins and bind to cognate receptors ...

Thyroid hormones are essential for skeletal development and bone maintenance. Childhood hypothyroidism causes growth arrest with delayed bone maturation, whereas thyrotoxicosis accelerates growth and advances bone age. In adults, thyrotoxicosis causes osteoporosis and increased susceptibility to fracture. To investigate mechanisms of T3 action in bone, we analyzed T3 receptor (TR) mutant mice. TRα-null (TRα0/0) mice are euthyroid but display delayed ossification with...

The Women's Health Initiative (WHI) trial and Million Women's Study (MWS) fundamentally changed our understanding of risks and benefits associated with HRT. WHI for the first time provided evidence of harmful effects of HRT on the cardiovascular system and also confirmed significantly increased risk of breast cancer previously documented in a meta analysis. HRT does not decrease, and may in fact increase, the incidence of ishaemic heart disease. The risk of stroke is increased...

All women with early onset oestrogen deficiency have an increased risk of cardiovascular disease regardless of aetiology, be it premature ovarian failure, hypopituitarism or Turner Syndrome. The fact that oestrogen deficiency in young women increases CVD risk appears to be in conflict with the adverse effects of oestrogen replacement on cardiovascular morbidity in postmenopausal women. One explanation for this paradox is that oestrogen may slow atherogenesis in young women whi...

The importance of endogenous hormones in the aetiology of breast cancer has long been evident from the strong relationships between breast cancer risk and certain aspects of a woman’s reproductive history1. More recently, the risk of developing breast cancer among postmenopausal women has also been shown to increase substantially with increasing levels of circulating oestradiol2, thus providing more direct evidence for the role of hormones in the development of the disea...

Receptors for insulin and insulin-like growth factor I (IGF-I) have been identified in endothelial cells derived from micro- and macrovessels. The insulin receptor in endothelial cells is structurally similar to that in other cell types and activation of its receptor tyrosine kinase leads to phosphorylation of insulin receptor substrate-1. In endothelial cells, insulin mediated activation of phosphatidylinositol 3-kinase (PI3K), Akt (protein kinase B)and the mitogen-activated ...