Endocrine Abstracts

Background: Obesity is a major medical health problem. Human brown adipose tissue (BAT) is potently activated by cold exposure and is a potential novel anti-obesity target. The current gold standard for measuring BAT activity in humans is 18F-FDG PET/CT. However it has two major limitations – exposure to ionizing radiation and high cost. Since BAT is a thermogenic organ located in the supraclavicular and neck regions, we hypothesised that an increase in tempera...

Background: Obesity is a global health concern. Elevating energy expenditure (EE) would be a highly effective treatment approach to treat obesity but no current drugs can safely achieve this. Cold exposure potently increases EE through brown adipose tissue (BAT) thermogenesis in humans. Glucagon elevates EE via BAT in rodents but the mechanism in humans is unknown. We investigated for the first time the mechanism by which glucagon increases EE in humans....

Background: Women with hypothalamic amenorrhoea (HA) have reduced LH pulsatility causing amenorrhea and infertility. Estrogen supplementation provides symptomatic relief for women with HA, but does not restore the pulsatile pattern of LH secretion which necessary for fertility. Kisspeptin-54 is a recently identified hormone, which potently stimulates GNRH secretion within the hypothalamus. The effect of exogenous kisspeptin-54 administration on LH pulsatility in women with HA ...

Background: The peptide hormone kisspeptin is essential for human reproduction, acting on the hypothalamus to stimulate GnRH secretion. Kisspeptin is emerging as a possible novel therapeutic for women with infertility. However animal studies suggest that kisspeptin may also stimulate pituitary secretion of GH, prolactin, and TSH, which has important implications for its safety. There has been no previous study investigating kisspeptin effects on non-reproductive hormones in hu...

Background: The KISS1 gene, is a critical regulator of normal reproductive function. In humans, KISS1 deletion results in a failure to go through puberty while activating mutations result in central precocious puberty. Administration of kisspeptin induces ovulation in rodents and sheep. However chronic exposure to exogenous kisspeptin-54 leads to profound tachyphylaxis in women with hypothalamic amenorrhoea. It is not known whether exogenous kisspeptin can alter the m...

Introduction: Kisspeptin-54 is a recently identified hormone, which potently stimulates GnRH secretion within the hypothalamus. Women with hypothalamic amenorrhoea (HA, hypogonadotrophic hypogonadism associated with low body weight) have reduced LH pulsatility causing amenorrhea and infertility. We have previously demonstrated that exogenous administration of kisspeptin-54 acutely stimulates gonadotrophin secretion in women with HA. However, it is not known whether exogenous k...

Background: Genetic deficiency of the hypothalamic hormone kisspeptin, lead to pubertal failure and infertility. Kisspeptin is therefore a critical hypothalamic activator of reproduction. Kisspeptin-10 stimulates gonadotrophin release in both male and female rodents. However few studies have investigated the effects of kisspeptin-10 on gonadotrophin release in humans, and none have investigated its effects in women. If kisspeptin is to be useful for treating reproductive disea...

Prokineticin 2 (PK2) is a neuropeptide expressed in hypothalamic nuclei involved in the regulation of energy homeostasis, and has been shown to acutely reduce food intake in rodents. PK2 binds to and activates two G protein-coupled receptors, the PK receptor 1 (PKR1) and the PK receptor 2 (PKR2). We aimed to determine the sites and receptors which mediate the anorectic effects of peripherally administered PK2 within the CNS. We investigated neuronal activity in the hypothalamu...

Background: Kisspeptin is a novel hypothalamic hormone with powerful stimulatory effects on the hypothalamo-pituitary–gonadal (HPG) axis. Inactivating mutations in the kisspeptin receptor lead to pubertal failure. We have previously demonstrated that injection of kisspeptin-54 stimulates LH release in healthy men and women. Recent studies in animals suggest that endogenous kisspeptin may be involved in stimulating the GnRH pulse generator. Determining whether exogenous ad...

Kisspeptin, the endogenous ligand of the GPR54 receptor, is a key regulator of the hypothalamo-pituitary-gonadal (HPG) axis. GPR54-null mice exhibit reproductive dysfunction and exogenous kisspeptin potently stimulates the HPG axis in rodents, primates and human males. The effects of kisspeptin administration to human females are not known.Aim: To investigate the effects of kisspeptin on luteinising hormone (LH) release during the menstrual cycle in fema...