Endocrine Abstracts

The 5′ UTR of the glucocorticoid receptor plays a key role in determining tissue specific expression, and protein isoforms. Analysis of the 5′ UTR of the hGR has revealed 11 splice variants of the hGR exon 1, based on 7 exon 1 s, 4 of which (1-D to 1-F and 1-H) were previously unknown. All of the exon 1 variants have unique splice donor sites and share a common exon 2 splice acceptor site. Due to an upstream in-frame TGA stop codon the predicted translation from al...

Patients with non-functional FOXE1 (forkhead transcription factor) display congenital hypothyroidism, ‘spikey’ hair and other abnormalities. In the thyroid, FoxE1 controls migration of the developing gland and adult expression of thyroid specific genes. Our earlier studies demonstrated FOXE1 protein expression in keratinocytes of the epidermis and hair-follicle outer root sheath.We aimed to characterise the expression and functional activity of...

Bone morphogenetic protein-2 (BMP-2) signal transduction requires heterocomplexing between type II receptors and different type I (α or β) receptors resulting in the activation of different signalling pathways. Previously, we have used αT3-1 and Lβt-2 cell lines, which are representative of different stages of gonadotroph development, to demonstrate differential expression of the receptor isoforms during gonadotroph maturation. BMPR-Iα and II mRNA and ...

In the ovary, 11βHSD enzymes inter-convert cortisol (F) with its inert metabolite, cortisone (E). Porcine follicular fluid from antral follicles and spontaneous ovarian cysts contains hydrophobic compounds that inhibit NADP(H)-dependent cortisol metabolism by 11βHSD1. The aim of this study was to measure intra-follicular F:E ratios in porcine antral follicles and ovarian cysts, and determine whether F:E ratios correlate with the inhibition of 11βHSD1 by porcine ...

Genome wide screens in Graves’ disease (GD) have identified several regions of linkage which may harbour genes which contribute to disease susceptibility. One such region, on chromosome 5q31-33, contains a cytokine cluster which includes interleukin-13 (IL-13). This molecule plays a key role in IgE production, which has been reported to be elevated in patients with GD. Two functional single nucleotide polymorphisms (SNPs), -1112 and +2044, within the IL-13 gene were recen...

Agouti-related protein (AGRP) plays a key role in energy homeostasis with the carboxy-terminal domain acting as an endogenous antagonist of the melanocortin-4 receptor (MC4-R). It has been suggested that the amino-terminal domain of AGRP binds to syndecan-3, allowing it to regulate local concentrations of AGRP at the MC4-R. This model assumes that AGRP is secreted as a full-length peptide. However, AGRP contains several consensus prohormone convertase cleavage sites: Lys52-Lys...

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3) is a potent antiproliferative agent with putative applications in the treatment of common cancers. However, doses of 1,25D3 required to achieve tangible anticancer responses also stimulate unwanted calciotropic effects. Data suggest that this is due, in part, to acquired resistance to 1,25D3 in cancer cells, particularly in more aggressive tumours. To investigate this fu...

The N-terminal fragment of human POMC consists of a 76 residue peptide (also known as pro-gamma-MSH) that contains the sequence of gamma-MSH in its C-terminus. Previous studies have demonstrated that the N-terminal portion not containing the gamma-MSH sequence is a potent adrenal mitogen while gamma-MSH itself can act synergistically with ACTH to increase steroid output.Since previous studies [1] have suggested that N-POMC 1-28 can stimulate the ERK path...

A 76 year old woman was referred in December 1997 to the Endocrine clinic at Luton & Dunstable Hospital following admission with atrial fibrillation which was managed by digoxin, flecainide and warfarin.Investigations initiated by her GP included reduced TSH at 0.18 milliUnits/Litre (0.32-5.00) despite normal free T4 of 14 picomols/Litre (9-24) and normal free T3 of 4.4 picomols/Litre (2.5-5.3). Ultrasound scan was in favour of multinodular goitre an...

Apparent Mineralocorticoid Excess (AME) resulting from liquorice ingestion is rare. Liquorice is still popular, however, and must be considered in the differential diagnosis of patients presenting with hypertension and hypokalaemia.A 62 year-old woman presented with refractory hypertension (blood pressure 200/118 mmHg) and hypokalaemic alkalosis (serum K 2.98 millimoles per litre; bicarbonate 30 millimoles per litre). There was no sign of Cushing's Syndr...