Endocrine Abstracts

Background: The hypothalamic neuropeptides kisspeptin and neurokinin B (NKB) are both obligate for normal gonadotrophin secretion. Studies in patients with loss-of-function mutations in NKB signalling suggest that kisspeptin is functionally upstream of NKB, but this hierarchy is unexplored in healthy men and women. We hypothesised that kisspeptin augmentation of estrogen-induced mid-cycle LH secretion will not be abrogated by pharmacological blockade of NKB.<p class="abste...

Context: IVF treatment is an effective therapy for infertility, but can result in the potentially life-threatening complication ‘ovarian hyperstimulation syndrome’ (OHSS).Objective: To investigate whether kisspeptin-54 can be used to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.Design: Phase 2 multi-dose open label randomised clinical trial.<p class...

Background: Self-limited delayed puberty (DP) often segregates in an autosomal dominant pattern, suggesting that inheritance is conferred by a small number of genes. However, the underlying genetic background is mostly unknown. By comparison, many genes have been identified where loss-of-function mutations lead to hypogonadotropic hypogonadism (HH). Despite likely overlap between the pathophysiology of delayed puberty and conditions of GnRH deficiency, few studies have examine...

The calcium-sensing receptor (CaSR), a class C G-protein coupled receptor (GPCR) is critical for calcium homeostasis. The presence of CaSR at the plasma membrane (PM) is regulated by a balance between internalisation via clathrin-mediated endocytosis, and agonist-induced PM insertion from intracellular receptor pools, in a mechanism known as agonist-driven insertional signalling. Recently, mutations of the clathrin-mediated endocytic adaptor protein-2 sigma subunit, AP2σ,...

Although the sodium iodide symporter (NIS) is expressed in 70–80% of breast cancers, only 20–30% is located at the plasma membrane (PM) and therefore functional. Previous work in thyroid cells leads demonstrated that PBF redistributes NIS from the PM into intracellular vesicles, potently reducing radioiodide uptake. We therefore examined whether increased membranous NIS could facilitate radioiodide therapy for breast cancer. Immunofluorescent microscopy revealed co-l...

Glucocorticoids (GC) are powerful metabolic hormones with anti-inflammatory effects. Exogenous GC are in wide therapeutic use but often cardio-metabolic side effects are limiting and resistance may develop. GC act via a nuclear hormone receptor (GR), which is a ligand activated transcription factor. GR binds DNA at sites distant from target gene promoters such as enhancers. Macrophages are ubiquitous innate immune cells that are major targets of GC and have roles in normal dev...