Endocrine Abstracts

MicroRNAs are highly conserved non-coding RNAs that regulate diverse cellular processes. Altered microRNA expression is observed in many human cancers and microRNAs may have tumour suppressor or oncogenic properties. One group of putative tumour suppressor microRNAs is the let-7 family whose expression is reduced in several human tumours, and which inhibit the expression of several oncogenes including HMGA2 and K-Ras. Let-7 expression have also been observed to b...

Delayed puberty may occur in some boys affected with X-linked Spondyloepiphyseal dysplasia tarda (SEDT), which is caused by mutations of the gene encoding a 140 amino acid protein designated Sedlin. Sedlin interacts with the pituitary homeobox 1 (Pitx1) and steroidogenic factor 1 (SF1) transcription factors, which are involved in the development and regulation of the hypothalamic-pituitary-gonadal axis. We have therefore investigated the hypothesis that SEDT associated mutatio...

The calcium-sensing receptor (CaSR) is a guanine-nucleotide-binding protein (G-protein)-coupled receptor that has a central role in calcium homeostasis. Loss-of-function mutations of the CaSR result in familial hypocalciuric hypercalcemia type 1 (FHH1) and gain-of-function mutations in autosomal dominant hypocalcemia (ADH). Recently, loss-of-function Gα11 mutations have been identified to cause FHH2 and we hypothesised that gain-of-function Gα11...

The multiple endocrine neoplasia type 1 (MEN1) gene, which when mutated gives rise to parathyroid, pancreatic and pituitary tumours, has been shown to have a role in embryogenesis, as Men1-null mice (Men1−/−) are embryonic lethal by 12.5 days post coitum (dpc). MicroRNAs (miRNAs) are emerging as potent regulators of early mammalian embryogenesis, and we therefore undertook expression profiling of miRNAs in Men1+/+ and M...

Mutations of the transcription factor GATA3, which is important for maintaining human breast luminal epithelial cell differentiation and quiescence, have been reported in 17 oestrogen receptor (ER) positive breast cancers, although the functional effects of these mutations have not been studied. We therefore investigated 56 ER-positive breast cancers for GATA3 mutations. The tumours were macrodissected, and immunohistochemistry for GATA3 revealed a strong correlation between E...

Glial cells missing B (GCMB), which is the mammalian homologue of the Drosophila GCM gene, encodes a 506 amino acid parathyroid-specific transcription factor that contains: a DNA-binding domain (residues 21–174); a predicted nuclear localization signal (residues 176–193); an inhibitory domain (residues 258–347); and two transactivation domains (residues 174–263, and residues 428–506). To date only two different GCMB m...

MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that negatively regulate gene expression through imperfect base pairing to the 3′ untranslated regions (UTRs) of target mRNAs. We have investigated the role of the miR-15a–miR-16-1 cluster in pituitary tumourigenesis, as it functions in other cancers as a tumour suppressor via regulation of the cell-cycle regulator cyclin D1. We have used two approaches: 1) in vitro studies examinin...

The calcium-sensing receptor (CaSR) plays a central role in regulating parathyroid hormone (PTH) secretion in response to changes in extracellular calcium. The CaSR is a G-protein-coupled receptor and ligand binding results in stimulation of phospholipase C (PLC) activity, causing accumulation of inositol 1,4,5-triphosphate (IP3) and the rapid release of calcium ions from intracellular stores. Given the pivotal role of the CaSR in calcium homeostasis, we decided to ...

The calcium-sensing receptor (CaSR) belongs to family C of G-protein coupled receptors (GPCRs) that bind glutamate, GABA, taste molecules and pheromones. Loss-of-function mutations of the CASR gene located on chromosome 3q21–24, cause familial benign hypocalciuric hypercalcaemia type 1 (FBHH1). The genes causing FBHH2 and FBHH3, whose chromosomal locations are on 19p and 19q13.3, respectively, remain unknown. FBHH3, sometimes called the Oklahoma variant (FBHHO...

(This poster is based on OC24)...