Endocrine Abstracts

Graves’ disease (GD) and Hashimotos’ thyroiditis (HT), two of the most common autoimmune thyroid diseases (AITD), are caused by both shared and disease specific genetic determinants. In females one copy of the X chromosome is randomly inactivated, and although inactivation should occur with a parent of origin ratio of 50:50, skewed X chromosome inactivation (XCI) can occur, whereby >80% of a specific copy of the X chromosome is inactivated. Increased skewed XCI i...

Graves’ disease (GD) affects >2% of the population and occurs more frequently in females than males. Several hypotheses have been put forward to explain the female preponderance including increased immune responsiveness, gonadal steriods, sex chromosome susceptibility loci and, more recently, skewed X inactivation (XCI). XCI occurs in females causing one of their X chromosomes to be randomly inactivated enabling dosage compensation with males who only have one copy of...

The pituitary tumor transforming gene binding factor (PBF) is a poorly characterised gene that is over-expressed in pituitary and thyroid tumours. Recently, we showed that subcutaneous expression of PBF elicits tumours in nude mice, and expression correlates with thyroid tumour recurrence in man. Given the established role of ionising radiation in thyroid tumourigenesis, we have now investigated the relationship between PBF and the tumour suppressor gene p53, a central compone...

The importance of thyroid hormone (TH) transporters to central nervous system (CNS) development has been highlighted by reports of severe global neurological impairment associated with mutations in the potent TH transporter, MCT8. Even subclinical maternal hypothyroidism in early pregnancy has been associated with long-term neurodevelopmental delay in the offspring suggesting that TH is crucial for early fetal brain development. The cellular entry of TH requires the function o...

The key mitotic regulator pituitary tumor transforming gene (PTTG) is expressed at low levels in fetal brain compared with adult, and modulates the proliferation of human embryonic neuronal N-Tera2 (NT2) cells. We examined the function and expression of PTTG’s interacting partner separase, along with Rad21, the functional component of cohesin, which is cleaved by separase following interaction with PTTG. In contrast to PTTG, the cleaved forms of separase and Rad21 were hi...

Introduction: Radioiodine (RI) is a safe and effective treatment for Graves’ disease. In the months following RI different strategies are used to gain control of thyroid status, although there is no evidence base as to the optimal approach.Objectives: To compare the incidence of dysthyroidism post-RI between three principal management strategies employed by clinicians.Study design and methods: Retrospective, observational, mul...

Dysregulation of the processing and stability of mRNA encoding oncogenes or tumour suppressor proteins is a critical event in the pathogenesis of cancer. Previously, we demonstrated that the proto-oncogene PTTG-binding factor (PBF) is overexpressed in thyroid, pituitary and breast tumours. Critically, high PBF expression is associated with reduced disease-specific survival in thyroid cancer. However, the mechanisms responsible for regulating PBF expression are unknown. In this...

PTTG1-binding factor (PBF) is an oestrogen-regulated proto-oncogene that is overexpressed in thyroid, breast and pituitary tumours. The precise role of PBF in tumourigenesis, however, has not been established, nor whether it is also an aetiological factor in non-endocrine cancer. In this study, we investigated PBF function in established colorectal cells and human tumours. Specific binding was evident between the tumour suppressor p53 and both endogenous and exogenous PBF in H...

Nodular thyroid disease is common and its pathogenesis remains poorly understood. Previously, we showed that thyroid-targeted overexpression of the proto-oncogene PTTG-Binding Factor (PBF) induced striking thyroid gland enlargement in transgenic mice (PBF-Tg)1. We have now investigated whether dietary factors influence goitrogenesis and the development of hyperplastic lesions in PBF-Tg mice. The mean weight of thyroids (5.8±0.9 mg; n=70) from 7 week old ...

Within the basolateral membrane of thyroid follicular epithelial cells, two transporter proteins are important for thyroid hormone (TH) biosynthesis. Initially, sodium iodide symporter (NIS) delivers iodide from the bloodstream into the thyroid and, following biosynthesis, monocarboxylate transporter 8 (MCT8) mediates secretion of TH from the thyroid gland. NIS-mediated radioiodine uptake is also critical in the treatment of thyroid tumours and metastases. We have previously d...