Endocrine Abstracts

Seasonal reproduction enables animals outside tropical regions to rear offspring in a favourable environment. Increasing day length triggers a hypothalamic relay involving thyrotropin, the type 2 deiodinase enzyme and thyroid hormone, which activates the hypothalamic-pituitary-gonadal axis to induce reproductive competence. Photoperiod regulates calcium metabolism and the egg-laying cycle in the Japanese quail (Coturnix japonica), and we hypothesised that activity of ...

Local and systemic bone loss is a common complication in patients with chronic inflammatory disease. Previously, we have identified that glucocorticoid (GC) activation by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is increased within tissues such as bone during systemic inflammation. However, whilst effective at suppressing inflammation, in excess, GCs drive osteoporosis. To determine the contribution of 11β-HSD1 activated glucocorticoids to inf...

Background: Despite a wealth of gene-discovery studies identifying recurrently mutated genes in hereditary and sporadic endocrine tumours, the molecular mechanisms underpinning tumourigenesis frequently remain ill-defined, in part reflecting a lack of physiologically relevant model systems to investigate gene function. Here, using pancreatic neuroendocrine tumours as an example, we explored the utility of human induced pluripotent stem cell (iPSCs) and CRISPR/Cas9 gene-editing...

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...

Maternal exposures during pregnancy to endocrine disrupting chemicals increase daughter’s breast cancer risk in humans and animal models. We have previously found that these exposures also pre-program offspring’s mammary tumors to exhibit increased resistance to antiestrogen therapy, and that treatment with valproic acid (HDAC inhibitor) and hydralazine (DNMT inhibitor) prevented antiestrogen resistance. Here we investigated if maternal exposure to ethinyl estradiol ...

Loss- and gain-of-function mutations of the calcium-sensing receptor (CaSR) cause familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemia (ADH), respectively. The CaSR is a homodimeric receptor that has a 612 amino acid extracellular domain (ECD), which binds extracellular calcium (Ca2+e) and mediates dimer interactions upon ligand binding. The ECD consists of lobes 1 and 2, and a cysteine-rich domain (CRD). To elucidate the struc...