Endocrine Abstracts

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...

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...

Background: IVF is an effective treatment for infertility, but can cause the ovarian hyper-stimulation syndrome (OHSS), which is associated with serous effusions, cardiac tamponade, circulatory collapse, and even death. Injection 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 physiological stimulus...

Background: Placentation (invasion of the placenta into the maternal endometrium of pregnancy known as the decidua) is hypothesised to be critical for healthy placental function and is abnormal in two thirds of miscarriage. Kisspeptin has emerged as a putative regulator of physiological placentation; it is highly expressed in placental syncitio-trophoblasts, whereas its receptor is expressed in both syncitio- and cyto-trophoblasts, such that kisspeptin is hypothesized to play ...

Background: Hypogonadotrophic hypogonadism is characterised by hypogonadism in the context of low/inappropriately normal gonadotrophin levels. Congenital Hypogonadotrophic Hypogonadism (CHH) occurs due to disrupted GnRH neuronal migration, or impaired hypothalamic GnRH secretion or action. However, no direct test of hypothalamic GnRH neuronal function currently exists. Kisspeptin-54 is a neuropeptide that stimulates endogenous hypothalamic GnRH release. Thus, we investigated w...

Background: Phaeochromocytomas (PCC) and paragangliomas (PGL) are neuroendocrine tumours that can secrete catecholamines. PCC are found in the adrenals, whereas PGL are found at any level between the skull base to the pelvis. More than 25% of cases are associated with mutations in susceptibility genes such as the SDH subunits. Screening for PCC/PGL crucially depends on detection of biochemical markers such as catecholamines and metanephrines (catecholamine metabolites).<p ...