Searchable abstracts of presentations at key conferences in endocrinology
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Society for Endocrinology BES 2014

ea0034oc5.1 | Pituitary | SFEBES2014

Increased frequency and earlier onset of pituitary tumours in mice deleted for a multiple endocrine neoplasia type 1 allele and null for prolyl hydroxylase domain protein 1 (Men1+/−/Phd1−/−)

Stevenson Mark , Piret Sian , Javid Mahsa , Bishop Tammie , Reed Anita , Walls Gerard , Gaynor Katie , Newey Paul , Christie Paul , Nicholls Lynn , Ratcliffe Peter , Thakker Rajesh

Cumulative genetic abnormalities within an oncogenic pathway may contribute to earlier onset or increased aggressiveness of cancers. An example in human and murine cancer is the dysregulation of Wnt signalling by inactivation of the adenomatous polyposis coli (APC) gene that results in accumulation of nuclear β-catenin and earlier onset of renal cell carcinoma, which can be accelerated by p53-deficiency. We therefore investigated the effects of such cumulative genetic abn...

ea0034oc5.2 | Pituitary | SFEBES2014

Implications of the upregulation of lysine specific demethylase 1 in the pathogenesis of pituitary adenomas

Thompson Iain , He Min , Clark Erin , Xu Shuyun , Tang Dan , Laws Edward , Shi Yujiang , Carroll Rona , Kaiser Ursula

The pathogenesis of pituitary adenomas is poorly understood. One of the first genetic abnormalities identified in association with pituitary adenomas occurs in patients with multiple endocrine neoplasia type-1 (MEN-1), due to mutations in the MEN1 gene, encoding menin. A tumor suppressor, menin associates with histone methyltransferase complexes to change the expression of cyclin-dependent kinase (CDK) inhibitor genes, which may serve as an underlying epigenetic mecha...

ea0034oc5.3 | Pituitary | SFEBES2014

The Wnt/β-catenin effector Tcf3/TCF7L1 is required for normal hypothalamic--pituitary development and mutation in this gene are associated to congenital hypopituitarism

Gaston-Massuet Carles , McCabe Mark , Dattani Mehul , Martinez-Barbera J P

Aberrant development of the pituitary gland can result in the clinical manifestation of hypopituitarism. The Wnt/β-catenin pathway has been shown to be involved in normal organogenesis, terminal differentiation and the aetiology of pituitary tumours. However, the specific developmental roles during hypothalamic–pituitary development of some of the Wnt/β-catenin effectors, such as Tcf3, have been hampered due to the early lethality of null embryos for th...

ea0034oc5.4 | Pituitary | SFEBES2014

GnRH pulse frequency-dependent regulation of ICER, a modulator of FSHβ transcription, is attenuated by MEKI/II blockade

Thompson Iain , Ciccone Nick , Xu Shuyun , Zhou Qiongjie , Zaytseva Sofiya , Carroll Rona , Kaiser Ursula

The pulsatile release of GnRH regulates the synthesis and secretion of pituitary FSH and LH. Two transcription factors, the cAMP response element binding protein (CREB) and inducible cAMP early repressor (ICER), have been implicated in the regulation of rat FSHβ gene expression. We hypothesized that CREB and ICER are activated by distinct signaling pathways in response to pulsatile GnRH to modulate FSHβ gene expression, which is preferentially stimulated at low (ever...

ea0034oc5.5 | Pituitary | SFEBES2014

Spatio-temporal analysis of prolactin gene transcription dynamics reveals short range co-ordination of lactotroph transcription activity in pituitary tissue

Featherstone Karen , Hey Kirsty , Momiji Hiroshi , McNamara Anne , Patist Amanda , Spiller David , Christian Helen , McNeilly Alan , Mullins John , Finkenstadt Barbel , Rand David , White Michael , Davis Julian

Mammalian genes display pulsatile transcription dynamics with bursts of expression occurring with variable duration and frequency. Using the human prolactin gene as a model of tissue specific gene regulation, we have characterised the transcription dynamics of this gene in cell lines, primary cells and pituitary tissue slices. Our data indicate that the tissue environment may have an important influence on cellular transcription activity. Cultures of cells from enzymatically d...

ea0034oc5.6 | Pituitary | SFEBES2014

A GH antagonist fusion with GH binding protein is biologically active, shows delayed clearance and inhibits growth in a rabbit model

Wilkinson Ian , Phipps Michael , Sayers Jon , Artymiuk Peter , Ross Richard

Background: Acromegaly is associated with increased morbidity and mortality, however currect medical treatment controls the disease in <60% of patients. Pegvisomant, a pegylated GH antagonist, controls the disease in over 95% of cases, but is not cost effective as it requires high dose daily injections and has side-effects. We have developed a technology for generating a long acting potent GH antagonist.Hypothesis: That a GH antagonist fused to GH bi...