Searchable abstracts of presentations at key conferences in endocrinology

ea0013oc18 | Novartis Clinical Endocrinology Award | SFEBES2007

Sedlin mutations disrupt interactions with pituitary homeobox 1 (Pitx1) and steroidogenic factor 1 (SF1): potential cause of delayed puberty in boys with Spondyloepiphyseal dysplasia tarda (SEDT)

Jeyabalan Jeshmi , Andrew Nesbit M , Ingraham Holly A , Thakker Rajesh V

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...

ea0034p8 | Bone | SFEBES2014

Liraglutide, a glucagon-like peptide-1 receptor agonist, improves bone mass and architecture in ovariectomised mice

Pereira Marie , Jeyabalan Jeshmi , Jorgensen Camilla Sofie , Cleasby Mark , Hopkinson Mark , Chenu Chantal

The increased incidence of type 2 diabetes mellitus (T2DM) among the aged is associated with an impaired skeletal structure and a higher prevalence for bone fractures. Besides, anti-diabetic therapies can also negatively affect bone mass. In this study, we tested the skeletal effects of chronic administration of two glucagon-like peptide receptor (GLP-1R) agonists and examined the expression of GLP-1R in bone tissue and cells. Twelve week-old female C57Bl/6N mice were ovariect...

ea0021oc2.2 | Neuroendocrine tumours/pituitary | SFEBES2009

Wnt/β-catenin signalling is down-regulated in pituitary tumours from a multiple endocrine neoplasia type 1 (MEN1) mouse model

Walls Gerard , Newey Paul , Nesbit M Andrew , Jeyabalan Jeshmi , Schulz Herbert , Huebner Norbert , Thakker Rajesh

The tumour suppressor menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, has been reported to be a component of the Wnt/β-catenin signalling pathway. To investigate the effects of menin loss on this pathway, we have determined the cDNA expression profiles of pituitary tumours from 5 Men1+/− mice and in normal pituitaries from 5 Men1+/+ littermates by extracting total RNA and by hybridizing it to Affymetrix Mous...

ea0021p304 | Pituitary | SFEBES2009

Pituitary tumours of mice deleted for a multiple endocrine neoplasia type 1 allele have alterations in apoptotic pathway components

Walls Gerard , Newey Paul , Jeyabalan Jeshmi , Nesbit A Michael , Schulz Herbert , Huebner Norbert , Thakker Rajesh

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of anterior pituitary, pancreatic islet and parathyroid tumours. Mice (Men1+/−) deleted for an MEN1 allele develop these tumours. The MEN1 gene encodes a 610 amino acid protein that has been reported to upregulate caspase 8 expression and promote apoptosis. To characterize the functional effects of menin loss in vivo, we asse...

ea0015p175 | Endocrine tumours and neoplasia | SFEBES2008

Assessment of in vivo proliferation rates in insulinomas of multiple endocrine neoplasia type 1 knockout mice: implications for evaluating effectiveness of future treatments

Walls Gerard V , Reed Anita AC , Harding Brian , Jeyabalan Jeshmi , Thakker Rajesh V

Pancreatic endocrine tumours (PETs) have a low proliferation index and this partially accounts for their lack of response to chemotherapy. The assessment of proliferation rates relies largely on the use of markers such as Ki67 in patients, and uptake of DNA nucleotide precursors such as tritiated thymidine or 5-bromo-2-deoxyuridine (BrdU) in animals. Amongst these, BrdU is recognised to be the most reliable marker of cell proliferation as it allows the substitution of an endog...

ea0015p180 | Endocrine tumours and neoplasia | SFEBES2008

Somatostatin producing cells are significantly decreased in insulinoma islets of multiple endocrine neoplasia type 1 (MEN1) knockout mice: implication for pancreatic proliferation rates

Reed Anita AC , Jeyabalan Jeshmi , Walls Gerard V , Harding Brian , Thakker Rajesh V

D cells comprise 3–10% of the human endocrine pancreas and secrete somatostatin, which inhibits cell proliferation and hormone secretion. Pancreatic tumours secreting somatostatin are associated with the somatostatinoma syndrome, which is characterised by hyperglycaemia, cholethiasis, a low acid output and anaemia. We have examined for the presence of somatostatin secreting cells in pancreatic tumours from a multiple endocrine neoplastic type 1 (MEN1) knockout mouse model...

ea0021oc3.6 | Young Endocrinologists prize session | SFEBES2009

Men1 gene replacement therapy using a modified adenoviral vector demonstrates reduced proliferation rates in pituitary tumours from mice deleted for a multiple endocrine neoplasia type 1 allelle

Javid Mahsa , Walls Gerard , Lemos Manuel , Jeyabalan Jeshmi , Bazan-Peregrino Miriam , Tyler Damian , Stuckey Daniel , Seymour Len , Thakker Rajesh

Multiple endocrine neoplasia type 1 (MEN1) is characterised by the combined occurrence of pituitary, pancreatic and parathyroid tumours. The MEN1 gene encodes a 610-amino acid tumour suppressor, menin, and MEN1-associated tumours show loss of heterozygosity. This indicates that replacement of the wild-type MEN1 gene may inhibit tumourigenesis. We have previously demonstrated that a recombinant adenoviral vector could be safely injected directly into pituit...

ea0034p406 | Thyroid | SFEBES2014

Hypoxic incubation favours the development and growth of primary human parathyroid adenoma cells

Lines Kate E , Stevenson Mark , Mihai Radu , Grigorieva Irina V , Baban Dilair , Gaynor Katherine U , Jeyabalan Jeshmi , Javid Mahsa , Thakker Rajesh V

Hypoxia is a primary stimulus for angiogenesis, which is important for tumour proliferation and survival. The effects of hypoxia on parathyroid tumour cells, which may be important for parathyroid autotransplantation in patients, are however, not known. We therefore assessed the effects of hypoxia on gene expression in parathyroid adenoma cells from patients with primary hyperparathyoridism. Cell suspensions from human parathyroid adenomas (n=5) were cultured and afte...

ea0021p19 | Bone | SFEBES2009

Hereditary renal calcification locus, Rcalc1, is associated with altered expression of cell survival genes

Loh Nellie Y , Stechman Michael J , Schulz Herbert , Jeyabalan Jeshmi , Reed Anita A C , Ahmad Bushra , Stewart Michelle , Brown Steve D M , Huebner Norbert , V. Thakker Rajesh

Renal stone disease is a common disorder for which the underlying causes remain largely unknown. We have investigated a hereditary renal calcification mouse model, Rcalc1, that is not associated with hypercalciuria for underlying mechanisms. Kidney RNA from 30 to 33 week-old Rcalc1 and control BALB/c and C3H female mice (n=4/group) was extracted and hybridised to Mouse Genome 430 2.0 arrays (Affymetrix). Following Robust Multichip Average normalization, pair-wise compar...