Endocrine Abstracts

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: 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...

Kisspeptin is a recently identified reproductive hormone which serves as a crucial activator of the Hypothalamic–Pituitary–Gonadal (HPG) axis via stimulation of GnRH neurones. We have previously observed that a single kisspeptin injection increases LH pulsatility while twice daily kisspeptin injections can even advance the menstrual cycle. Furthermore, we have demonstrated that kisspeptin restores LH pulsatility in women with hypothalamic amenorrhoea and can potently...

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: Miscarriage is the spontaneous loss of pregnancy occurring prior to 24 weeks of gestation, and can be devastating for affected couples. Abnormal placental development is observed in two-thirds of miscarriages. Recently, the circulating placental markers kisspeptin, prokineticin-1 (PK-1), soluble fms-like tyrosine kinase-1 (sFlt1), soluble endoglin (sEng) and placental growth factor (PlGF) have been identified and investigated for potential associations with miscarr...

Background: In vitro fertilisation (IVF) is an effective treatment for infertility, but can cause the ovarian hyper-stimulation syndrome (OHSS), which is associated with serous effusions, circulatory collapse, and even death. The use of human chorionic gonadotrophin (hCG) stimulates oocyte maturation during IVF, but is also the major cause of OHSS. The hypothalamic neuropeptide kisspeptin stimulates endogenous LH secretion in a GnRH-dependent manner. A more physiologi...