Endocrine Abstracts

Clinical Endocrinology 2016 84 939–945. DOI: 10.1111/cen.12603...

Clinical Endocrinology 2016 84 939–945. DOI: 10.1111/cen.12603...

Hypoactive sexual desire disorder (HSDD) is a persistent lack of sexual desire, causing marked interpersonal distress. It is the most common global female sexual health problem, although the precise pathophysiology remains uncertain. Existing treatment options are limited by their efficacy and side effects. The neuropeptide kisspeptin offers a potential therapeutic target given its emerging role in modulating reproductive behaviour. Using a combination of psychometric, neuroim...

Background: There is emerging evidence that kisspeptin, a hormone with well-established reproductive effects, may also have important metabolic effects. Acute kisspeptin administration enhances insulin secretion under hyperglycaemic conditions in male rodents and men, and kisspeptin receptor agonism improves steatohepatits in male mice in a rodent model of non-alcoholic fatty liver disease. However, the metabolic effects of kisspeptin may exhibit sexual dimorphism as female (b...

Background: Placentation (invasion of the placenta into the maternal endometrium) is hypothesised to be critical for healthy placental function and is abnormal in two thirds of miscarriages. Kisspeptin has emerged as a putative regulator of physiological placentation; it is highly expressed in placental syncytiotrophoblasts and could play an important paracrine role in the regulation of placentation. Circulating kisspeptin levels are considerably raised during healthy pregnanc...

Introduction: Hypothalamic amenorrhoea (HA) is a condition characterised by reduced GnRH pulsatility and is a common cause of anovulatory subfertility. Kisspeptin is an endogenous neuropeptide that regulates hypothalamic GnRH function. Hypothalamic kisspeptin expression is reduced, and kisspeptin receptor expression is increased, in a rodent model of HA. The kisspeptin analogue MVT-602 has a 3-4-fold longer half-life than native kisspeptin-54 (t1/2 0.5 h). We invest...

Background: Hypothalamic KNDy neurons have recently been identified as key regulators of reproductive function by releasing three neuropeptides namely kisspeptin, neurokinin B (NKB) and dynorphin. Animal studies show they interact to control pulsatile GnRH release, which is vital for fertility. In animals, kisspeptin stimulates, NKB modulates and the opioid dynorphin inhibits GnRH pulsatility. However, the interaction of these peptides has never been studied in humans. To inve...

Background: In vitro fertilisation is an effective therapy for infertility, but can result in the potentially life-threatening complication, Ovarian Hyper-Stimulation Syndrome (OHSS). We have previously reported that a single injection of kisspeptin results in an LH surge of ~12–14 hrs duration, sufficient to safely induce oocyte maturation, but eliminate OHSS. However, the physiological LH surge in a normal menstrual cycle has a plateaux lasting 24–28 hrs. ...

Background: Hypogonadotrophic Hypogonadism (HH) is characterised by hypogonadism in the context of low gonadotrophin levels, frequently due to a defect in hypothalamic function e.g. Kallman’s syndrome. However, no direct test of hypothalamic function currently exists. Kisspeptin is a hypothalamic neuropeptide that stimulates endogenous GnRH release. Thus, we investigated whether kisspeptin could be used to interrogate hypothalamic function in men with HH.<p class="abs...

Background: Kisspeptin-54 (KP54) stimulates hypothalamic GnRH release. The kisspeptin analogue, MVT-602, has a longer half-life (t1/2108min) than KP54 (t1/228mins). MVT-602 potently stimulates gonadotrophin release in men. We sought to determine for the first time the effect of MVT-602 on gonadotrophin release in healthy women.Methods: A two-phase dose-finding study was carried out in 9 healthy women, 18–35 yrs with regular men...