Endocrine Abstracts

Background: Patients with complete androgen insensitivity syndrome (CAIS) who undergo gonadectomy have evidence of reduced bone mineral density (BMD) and perhaps, higher risk of fragility fractures. Because of this, hormonal replacement therapy (HRT), usually in the form of estrogen, is used as patients with CAIS have 46, XY genotypes having androgen receptor abnormalities making them resistant to the effects of androgen. Tibolone, a “selective tissue estrogenic activity...

Locus-specific databases (LSDBs) have been recently developed in response to the increasing number of genetic changes reported in the human genome. LSDBs have been created for several genes implicated in endocrine syndromes, for example MEN1, VHL, RET, GNAS, PRKAR1A and the SDH subunits. Mutations in AIP are found in about 20% of familial isolated pituitary adenoma (FIPA) patients.The aim of this proj...

Glucocorticoids (GCs) are highly effective anti-inflammatory drugs, however their use is limited by serious side effects. We have previously shown that 5αTHB binds GC receptor (GR) and suppresses inflammation in vitro and in vivo, without affecting metabolism. Here the underlying molecular mechanisms were explored in cell models of ligand-induced GR phosphorylation, nuclear localisation and gene transcription. Data are mean±S.E.M. (th...

Circulating levels of prolactin are subject to acute and long-term regulation by many factors including oestrogen and dopamine. We have studied the regulation of prolactin promoter activity in living pituitary cells using transgenic Fischer rats in which reporter gene expression is regulated by the human prolactin gene locus (hPRL-d2EGFP). We have previously identified pulsatile prolactin transcription patterns in living lactotroph cells in fetal tissue, that became stabilised...

Background: Primary Aldosteronism (PA) is common and associates with excess cardiovascular morbidity independent of blood pressure. Animal and in vitro studies have demonstrated that exposure to aldosterone and sodium leads to cardiac fibrosis and hypertrophy and this may, partly, be mediated by inflammation and oxidative stress. We aimed to clarify the effects of aldosterone excess on myocardial structure and composition in humans using contrast-enhanced cardiac MRI as well a...

Understanding how fate choices are made by multipotent progenitors during pancreas development is valuable information in the quest for regenerative medicine and cell therapy to treat diabetes mellitus. Pancreatic differentiation is well defined and understood in rodents however, human data are comparably scarce. Specifically, when human pancreatic progenitors are multipotent is unknown as are the epigenetic changes that these cells undergo during their differentiation to beta...

Background: Classic 21-hydroxylase deficiency (21HD) presents some traits of the metabolic syndrome. We aimed to characterize discrete alterations of lipid and carbohydrate metabolism in children and young adults with classic 21HD, which could predict early atherogenesis.Design: Cross-sectional comparative.Patients and methods: Of 27 Caucasian patients with classic 21HD (4–31 years); 27 sex-, age- and BMI-matched controls. Cli...

Hypopituitary patients are at increased vascular risk. This may be partly attributable to changes in insulin action. It has been suggested that the addition of dehydroepiandrosterone sulphate (DHEAS), which is low in patients with secondary hypoadrenalism, to routine replacement may have beneficial effects on glucose metabolism. Previously, patient populations and techniques used to assess insulin action varied and overall results have been conflicting.W...

Pituitary development, in particular the differentiation of anterior pituitary endocrine cells, remains to be fully understood, and may have implications for adult pituitary plasticity and hyperplasia. We have used prolactin-reporter transgenic rats to characterise prolactin transcription during the appearance of newly formed lactotroph cells during fetal development.Transgenic rats with the firefly luciferase reporter gene inserted into exon 1b of a 160...

Prolactin (PRL) is a hormone mainly produced by the lactotroph cells of the anterior pituitary gland. Besides its pivotal role in reproduction, PRL has also been found to have immuno-modulatory properties. The pituitary is the main source of circulating PRL, however it is also expressed in humans at extra-pituitary sites1. In extra-pituitary tissues, PRL mRNA contains an extra exon (exon 1a), and expression is regulated by an alternative promoter upstream of the pit...