Endocrine Abstracts

Kisspeptin is a crucial activator of reproductive function, playing a critical role in the hypothalamus to activate GnRH neurons and downstream reproductive hormones. However, kisspeptin and its receptor are also expressed in other brain areas, yet little is known about their function here. The limbic system plays a key role in sexual and emotional behaviours and has a high expression of kisspeptin receptors. We therefore hypothesised that kisspeptin administration may modulat...

MLE4901 (previously AZD4901) is a potent and selective neurokinin 3 receptor (NK3R) antagonist being developed for the treatment of polycystic ovary syndrome (PCOS). Clinical studies indicate the compound negatively regulates the hypothalamus-pituitary-gonadotropin (HPG) axis to reduce pituitary luteinizing hormone and gonadal sex steroids. To understand the longer-term in vivo effects of MLE4901, a 13-week safety study was carried out. Groups of 3 male and female dog...

Background: Turner syndrome (TS) comprises a group of sex chromosome anomalies affecting approximately 15,000 in the UK. TS affects every organ system in the body through haploinsufficiency of genes that are normally expressed by both X chromosomes. Common features include short stature, congenital heart diease and gonadal dysgenesis requiring long-term oestrogen replacement but the adult phenotype extends to excess risk of diabetes, hypertension and hepatosteatosis. UCLH has ...

The gonadotrophin receptors, luteinising hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR) are G-protein coupled receptors, vital in regulating reproductive functions. Whilst FSHR and LHR are known to form homomers, and have been recently shown to heterodimerise/oligomerise, the functional and physiological significance of LHR/FSHR heteromerisation remains elusive. This study aimed to explore the functional significance of LHR/FSHR crosstalk, exploring me...

Background: Ipilimumab is a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor that improves survival in advanced melanoma. However, ipilimumab induces immune-related adverse events including hypophysitis and hypopituitarism. We describe one of the largest single centre series of ipilimumab induced hypophysitis.Methods: We retrospectively analysed all patients (n=301) treated with ipilimumab either as a monotherapy or in combination with nivolu...

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with anovulatory infertility, menstrual disturbances as well as an adverse metabolic profile. Although the pathophysiology of PCOS remains unclear, dysregulation of gene expression has been previously shown in theca and granulosa cells (GC). However, there has been no comprehensive analysis of steroidogenic gene expression in GCs from women with PCOS. In this study, we performed a comprehensive gene...