Endocrine Abstracts

Background: Cystic Fibrosis-related bone disease (CFBD) increases morbidity and mortality. Treatment varies across UK CF centres. Dual-energy X-ray absorptiometry (DEXA) is used for bone mineral density (BMD) evaluation: CFBD is diagnosed when Z-score<-2. European Cystic Fibrosis Society (ECFS) criteria for prescribing bisphosphonates:1. Presence of low-trauma fracture 2. Lumbar spine/ total hip/femoral neck Z-score <-2 and significant bone loss ...

Equine chorionic gonadotrophin (eCG) is not only essential for the maintenance of early equine pregnancy but is also used therapeutically for synchronisation of farm and laboratory animals. Currently it is extracted from serum of farmed pregnant mares. We have recently reported that under normoxic conditions, BMP4 treatment of equine trophoblast resulted in a dose, and developmental stage-dependent increase in total number of differentiated binucleate cells that secrete eCG. O...

Key genetic contributors are recognised to underlie the phenotype of central precocious puberty (CPP), including the imprinted genes Makorin ring finger protein 3 (MKRN3) and Delta-like homolog 1 (DLK1), alongside Kisspeptin-1 (KISS1) and (KISSR1). These genes have implicated mis-regulation of transcriptional control of the kisspeptin and gonadotropin-releasing hormone (GnRH) neuroendocrine systems in onset of CPP. However, many familial cases of CPP remain without clear a gen...

Mutations in each of the 4 subunits of succinate dehydrogenase (SDH) – SDHA, B, C and D predispose to development of phaeochromocytomas and paragangliomas. Loss of SDH function leads to accumulation of succinate which acts as an oncometabolite to drive tumourigenesis. However, mutations in SDHB have an increased likelihood of causing metastatic disease, compared to mutations in the other SDH subunits. The reasons behind this increased risk remai...

Familial glucocorticoid deficiency (FGD) is characterised by isolated glucocorticoid deficiency with retention of normal mineralocorticoid production. FGD causing mutations in the MC2R accessory protein, MRAP, often occur at the canonical donor splice-site of intron 3, presumed to result in skipping of the first coding exon with unknown consequences at the protein level. DNA from three patients (0 - 6 months) with high ACTH and/or low cortisol levels underwent whole e...

Effective treatment of differentiated thyroid cancer relies on a multifaceted approach often including administration of 131I to ablate residual cancer cells post-surgery. The success of this treatment hinges upon adequate uptake of iodide by malignant thyroid follicular cells. In a subset of patients, dedifferentiation of the carcinoma can result in aberrant expression and trafficking of the iodide transport protein, the sodium iodide symporter (NIS), resulting in ...

Equine Chorionic Gonadotrophin (eCG) is a heterodimeric glycoprotein produced by terminally differentiated, bi/multi-nucleate trophoblast cells in the placenta of horses and humans. It is responsible for the maintenance of early pregnancy via rescue of the corpus luteum and subsequently promotion of progesterone production. The beta subunit of eCG is expressed at levels ten-fold lower than that of the alpha subunit and confers the glycoproteins specificity to the placenta. Ver...

Placental chorionic gonadotrophin (CG) hormone secretion, critical for maintenance of early pregnancy, is dependent on differentiation of specialised CG-secreting binucleate trophoblast (horse) and syncytiotrophoblast (human). The most abundant genes expressed by binucleate cells are the α and β subunits of equine CG. We recently showed the transcription factor glial cells missing 1 (GCM1) is rapidly induced during differentiation of binucleate trophoblast and mRNA e...

Whilst the majority of differentiated thyroid cancers (DTC) have oncogenic mutations, a significant minority may be driven by the overexpression of proto-oncogenes. PTTG and PBF are proto-oncogenes which are induced in DTC, elicit tumours in xenograft models and interact in vitro, where PBF shuttles PTTG into the nucleus. However, the relative contributions of each gene to DTC has not been delineated. Here, we constructed a bi-transgenic murine model over-expressing b...

Pituitary tumor transforming gene (PTTG) is a multifunctional oncogene implicated in the pathogenesis of pituitary and thyroid tumours. In breast cancer, PTTG expression is a prognostic marker for lymph node invasion and tumour recurrence. PTTG expression is regulated in vitro and in vivo by oestrogen treatment. PTTG binding factor (PBF) is also a transforming gene, and was isolated due to its functional interaction with PTTG. In the current study, we examined PB...