Endocrine Abstracts

Circulating oestrogen concentrations affect the incidence of and outcomes for patients with colorectal cancer (CRC). We have previously shown that steroid sulphatase (STS), the fundamental enzyme that liberates conjugated oestrogens into their active forms, is significantly elevated in human CRC tissue. Here we demonstrate that elevated STS activity correlates to increased CRC proliferation, and that these effects are mediated through G-protein coupled oestrogen receptor (GPER...

Objectives: Oestrogen analysis using liquid chromatography mass spectrometry is problematic, as oestrogens do not readily ionise. This coupled with low concentrations in men, pre-pubertal and post-menopausal women provides an analytical challenge. We investigated N-Methyl Pyridine-3-sulfonyl chloride (NMPS) derivatisation, as described by Wang et al. (Steroids 2015 Apr;96:140-152) to improve sensitivity of 11 oestrogens; oestrone (E1), oestradiol (E2), 2-hydroxy-oestr...

Steroid profiling of biological fluids has been used for clinical and diagnostic research since the 1950s. Most methods focus on blood and urine, however, more recently saliva analysis has been employed as a non-invasive, simple to collect sample for the diagnosis of conditions such as Cushing’s and androgen excess. Despite its ease of collection, saliva remains an underutilised biofluid. To investigate the use of salivary steroid profiling for endocrine research, we aimed to ...

Oestrogenic effects on colorectal cancer (CRC) incidence, proliferation, and patient survival remains controversial. We have previously shown enzymic pathways favouring oestradiol (E2) synthesis are upregulated in CRC, and stimulation of the G-protein coupled oestrogen receptor (GPER) by E2 increases CRC proliferation. Here we interrogated The Cancer Genome Atlas (TCGA) Colon Adenocarcinoma (COAD) database to determine all oestrogen metabolism enzymes and...

Oestrogenic effects on colorectal cancer (CRC) incidence, proliferation, and patient survival remains controversial. We have previously shown enzymic pathways favouring oestradiol (E2) synthesis are upregulated in CRC, and stimulation of the G-protein coupled oestrogen receptor (GPER) by E2 increases CRC proliferation. Here we interrogated The Cancer Genome Atlas (TCGA) Colon Adenocarcinoma (COAD) database to determine all oestrogen metabolism enzymes and...

Oestrogen quantification in serum is challenging as concentrations are low, especially in men and post-menopausal women. Additionally, oestrogens do not ionise readily and structure similarities can lead to cross-reactivity and reduced specificity, especially with immunoassay. Full characterisation of oestrogen metabolism and its role in disease progression has therefore not been fully investigated. We aimed to develop and validate a liquid chromatography mass spectrometry met...

Gas chromatography–mass spectrometry (GC–MS) has been used for urinary steroid analysis for over 50 years. The process of hydrolysis to release steroids from their conjugates is routinely performed using commercially available snail Helix-Pomatia sulfatase (HP). However, as this is a naturally occurring enzyme its production process results in batch variation and so each batch requires experimental validation to adjust for the difference in efficiency of the enzymati...

Colorectal cancer (CRC) is the 2nd most commonly diagnosed cancer in Europe. Previously, we have shown steroid sulphatase (STS), the enzyme that converts conjugated oestrogens to their active forms, is significantly upregulated in human CRC tissue. Furthermore, increased STS activity substantiates greater CRC tumour burden in mouse models. Here we demonstrate that this oestrogen-induced increase of CRC proliferation is mediated by G-protein coupled oestrogen receptor (GPER) vi...

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 ...