Endocrine Abstracts

Ga-68 labelled urea-based inhibitors of the prostate specific membrane antigen (PSMA), such as 68Ga-HBED-PSMA-11, are promising peptides for targeting prostate cancer. The tris(hydroxypyridinone) (THP) ligand rapidly complexes 68Ga3+ at room temperature, at very low concentration and over a wide pH range, making it possible for the direct elution from a 68Ge/68Ga generator into a cold radiopharmaceutical kit in one step wi...

Background: Impaired Insulin-like growth factor-1 (IGF-1) function is associated with obesity and hypertension, but the correlation of circulating IGF-1 with these conditions is weak. As a metabolite of IGF-1, the ratio of cGP/IGF-1 regulates IGF-1 bioavailability and may be a more accurate biomarker of IGF-1 function in obesity and hypertension.Methods: Using ELISA and HPLCms methodologies, we analysed plasma concentration of IGF-1, cGP and IGFBP-3 in 4...

In patients with autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion; patients on long-term steroid replacement have increased morbidity, reduced life expectancy and poorer quality of life. Recent early-phase studieshave demonstrated that some endogenous steroidogenic function – Residual Adrenal Function (RAF) - is maintained at the point of diagnosis in a proportion of AAD patients; this...

In human prostate, Oestrogen receptor α (ERα) expression in the epithelium increases with tumour Grade and promotes proliferation involving classical genomic and rapid non-genomic signalling, as well as transcription regulation of non-coding RNA. Similarly, in the tumour stroma there is up-regulation of ERα, corresponding with declining AR, resulting in a higher ratio of ERα:AR with increasing Grade. Additionally, in prostate cancer-associated fibroblasts (...

Context: In rodents, in-utero exposure to the exogenous oestrogen diethylstilboestrol (DES) results in reproductive abnormalities in male offspring. It has been proposed that similar anti-androgenic effects also occur in the human fetal testis following oestrogen exposure.Objective: Determine effects of DES exposure on testosterone production by normally growing human fetal testis xenografts.Design: Human fetal testes (15&...

Despite lifelong glucocorticoid and mineralocorticoid replacement, there is excess morbidity and mortality associated with autoimmune Addison’s disease (AAD). Adrenal cortical cells undergo continuous self-renewal from a population of subcapsular progenitor or stem cells, under the influence of ACTH. We aimed to determine if synthetic ACTH analogue could revive adrenal steroidogenic function and ameliorate AAD.We performed an open-label trial of syn...

Background: Endocrine disruption in the human fetal testis by environmental agents has been proposed as a possible cause of testicular dysgenesis syndrome (TDS) comprising male reproductive disorders such as testicular germ cell tumours (TGCT), cryptorchidism, hypospadias and low sperm counts. Exposure of fetal rats to the widely used plasticizer di(n-butyl) phthalate (DBP) results in a TDS-like syndrome due to a reduction in testosterone production. Whether such effects also ...

Peroxisome proliferator activated receptor gamma (PPARγ), a ligand-inducible transcription factor, is essential for adipocyte differentiation and lipogenesis. We previously described a kindred in which some individuals were heterozygous for a frameshift/premature stop mutation, (A553ΔAAAiT)fs.185(stop186) in PPARγ, with the truncated protein being non-functional and lacking dominant negative activity1. PPARγ null heterozygotes had norm...

Leptin and adiponectin are cytokine-like hormones secreted by white adipose tissue. Plasma leptin correlates closely with total body fat mass, and its secretion is positively regulated by insulin in vivo and in vitro. Hypoleptinaemia is a key centrally-mediated orexigenic stimulus. Plasma adiponectin, in contrast, correlates negatively with whole body fat mass and insulin resistance in adults, and its expression is regulated negatively by insulin in vivo a...

Kisspeptin is a 54 amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates the G-protein-coupled receptor, GPR54. The kisspeptin/GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy but levels in gestational trophoblastic neoplasia (GTN) have not previously been reported. The...