Endocrine Abstracts

Central nervous system neurones are generally incapable of regenerating their axons after injury due to the limited availability of neurotrophins, the development of a glial scar, and the presence of multiple axon growth inhibitors. We therefore designed short interfering RNA (siRNA) sequences to knock down components of the inhibitory signalling cascade and tested their ability to disinhibit the growth of FGF2-stimulated dorsal root ganglia neurone (DRGN) neurites in the pres...

Calcium homeostasis is a key element in bone development and in the maintenance of normal bone architecture. Bone acts in conjunction with the kidneys and the parathyroid glands to maintain circulating calcium levels. In times of excess it functions as a reservoir, but it is also able to donate calcium to the body when circulating levels are low and its structure and mineral content vary accordingly. The calcium sensing receptor (CaR) in both the parathyroid glands and in the ...

With the cloning of the gene encoding pro-opiomelanocortin (POMC) it became apparent that several other peptides distinct from ACTH would be co-secreted from the anterior pituitary into the circulation. This begged the question as to whether these peptides have any biological actions on the adrenal, or to that matter any other tissue. Over the past two decades it has become apparent that the N-terminal fragment known as pro-gamma-MSH plays a role in adrenal physiology.<p c...

Prolactin is produced by pituitary lactotrophic cells and by several extrapituitary tissues, including immune cells and the endometrium in man. It has a wide range of actions at different sites, and hyperprolactinaemia and prolactinomas give rise to common clinical problems. The human prolactin gene contains six exons, with two distinct promoters that direct pituitary or extra-pituitary transcription respectively. The pituitary-specific promoter extends over 5000 base-pairs an...

In humans only thyroid hormone (T3) receptor (TR) beta1 and beta2 mRNAs have been identified, whereas alternative splicing generates recently characterised beta3 and deltabeta3 transcripts in rat and further N-terminal isoforms in other species. We investigated whether additional transcripts arise from the human TRbeta gene by 5'-RACE. Five distinct TRbeta1 transcripts were isolated, including the previously described TRbeta1 mRNA and four novel 5'-untranslated region (5'-UTR)...

Dent's disease is an X-linked renal tubular disorder characterised by low molecular weight proteinuria, hypercalciuria, and nephrolithiasis. The disease is caused by inactivating mutations of a renal-specific chloride channel, hCLC-5, that belongs to the family of mammalian voltage-gated chloride channels (CLCs). Heterologous expression of wild-type CLC-5 in Xenopus oocytes results in chloride (Cl-) conductance, which is markedly reduced or abolished by the m...

Increased mortality in patients with acromegaly has been confirmed in a number of retrospective studies, but causative factors and relationship to serum IGF1 remain uncertain. The West Midlands Acromegaly database contains details of 419 patients (178 males). Serum IGF1 data from the Regional Endocrine Laboratory was available for 338 patients (81%). At diagnosis mean age was 47 years (range 12-84) and mean GH was 70plus/minus5.4 milliunits per litre. 61% were treated by surge...

Oestrogens affect fluid balance, influencing both ingestive behaviour and renal excretion. The renal effects are partly due to altered release of the neurohypophysial hormones vasopressin and oxytocin and involve oestrogen receptor beta (ERbeta). Normal rat maintenance diet contains soya isoflavones (phytoestrogens) which are also known to act at ERbeta. A study has been performed comparing the fluid balance and neurohypophysial hormone release in rats maintained for two weeks...

The glucocorticoid receptor antagonist, RU486, binds to the glucocorticoid receptor (GR) with high affinity, and allows both nuclear localisation and also DNA binding. However, the DNA bound GR does not activate target gene transcription. This suggests that the ligand-binding domain of the GR is required to interpret agonist and antagonist ligands, and transmit those signals to the basal transcriptional machinery. Adaptor proteins play an important role in transducing the effe...

A 53 year old man with ANCA-positive glomerulonephritis was referred with a 3-month history of hypercalcaemia. There was no significant family history and treatment consisted of Maxepa concentrated fish oils 5g/day for glomerulonephritis and lansoprazole plus Bisodol (proprietary indigestion preparation containing calcium, magnesium and sodium bicarbonate) for a hiatus hernia. Investigations revealed a corrected calcium concentration of 3.06 mmol/l, phosphate 1.27 mmol/l, crea...