Endocrine Abstracts

Introduction: Use of degludec [tresiba] in children and adolescents with type 1 diabetes was approved by EC 2015 and FDA in December 2016. Degludec is a new ultra-long acting basal insulin with terminal half-life of approximately 25 hours and duration of action of more than 42 hours. Constant release of insulin throughout the day leads to better control of blood glucose for more than 24 hours with significant reduction in HbA1c.Aim: To compare and assess...

Steroid sulphatase (STS) liberates sulphated oestrogens into their active forms. In the colon, evidence suggests that although initially pro-apoptotic in healthy mucosa, once malignancy occurs, oestrogens may stimulate colorectal cancer (CRC) proliferation. Moreover, greater intratumoural oestrogen synthesis is negatively associated with survival outcomes in CRC patients. However, little is known about oestrogen metabolism pathways in CRC, and whether alterations in local oest...

Steroid sulphatase (STS) is the primary enzyme for desulphating steroids from their inactive to their active forms. Principal substrates include steroid precursors oestrone-sulphate and dehydroepiandrosterone sulfate. Alterations in STS activity can directly affect local concentrations of oestradiol, testosterone and dihydrotestosterone; steroids that are frequently dysregulated in disease. Despite the importance of STS activity on steroid synthesis, little is known about its ...

Colorectal cancer (CRC) is the third most common cancer worldwide with incidence expected to rise. Although not traditionally viewed as a hormonal cancer, evidence suggests peripheral synthesis of active oestrogens worsens prognosis. Oestrogen metabolising enzymes include steroid sulphatase (STS), which desulphates oestrogens into their active forms, and 17β-hydroxysteroid dehydrogenases (17βHSD), which are estrogen oxidoreductase enzymes. We have previously shown ST...

Although not normally considered an oestrogen responsive tissue, compelling evidence now exists suggesting that the colon is responsive to oestrogenic effects. Results from the Women’s Health Initiative demonstrated that post-menopausal women taking oestrogen and progestins as hormone-replacement therapy (HRT) had a 40% reduction in developing colorectal cancer (CRC). Intriguingly, patients taking oestrogen supplements at the time of CRC diagnosis presented a much more ad...

Many post-doctoral scientists still believe that the road to academic success follows the traditional university career trajectory. Although some lectureship and fellowship positions will inevitably be filled by those who have chosen this path, forward-thinking universities now seek principal investigators who have international collaborations and industry links, supported by unique expertise and knowledge on many divergent aspects of scientific research. But as the economic d...

Colorectal cancer (CRC) is the third most common cancer and is one of the highest incidences and mortality tumours worldwide. Our group has previously shown that CRC favours oestradiol synthesis by increasing steroid sulfatase (STS) activity and altering 17β-hydroxysteroid dehydrogenases (HSD17Bs) expression. However, what regulates STS activity and HSD17Bs expression and activity in CRC remains unknown. In breast and prostate cancer inflammatory mediators, such as TNF&#9...

Oestrogens impact colorectal cancer (CRC) development and proliferation. Biologically active oestrogens, oestrone (E1) and oestradiol (E2), are metabolised through hydrolysis of their sulfated forms (oestrone sulfate (E1S) and oestradiol sulfate) by steroid sulfatase (STS). We have shown that increased STS activity drives CRC proliferation via oestrogen hydrolysis. We have also identified that CRC expresses the necessary organic anion transport...

The production of oestradiol (E2) is paramount for the growth of oestrogen receptor α positive breast cancer. Various strategies have been used, including the use of enzyme inhibitors against either aromatase (AROM) or steroid sulphatase (STS), in an attempt to ablate E2 levels. Both these enzymes play a critical role in the formation of oestrogenic steroids (see figure 1) and their inhibitors are now showing success in the clinic. The studies presented here demonstrate t...

A 74-year-old gardener developed progressive dysphagia for solids and liquids over 15 months. He lost five stone in weight and became increasingly weak. There was nothing significant in his past medical and drug histories. He is married, never smoked and drank little alcohol.He had an acute medical admission via A&E in April 2008 for profound dehydration and cachexia. His weight was 41.5 kg. There were no gross neurological deficits but he had hoarse...