Endocrine Abstracts

Background: Self-limited delayed puberty (DP) often segregates in an autosomal dominant pattern, suggesting that inheritance is conferred by a small number of genes. However, the underlying genetic background is mostly unknown. By comparison, many genes have been identified where loss-of-function mutations lead to hypogonadotropic hypogonadism (HH). Despite likely overlap between the pathophysiology of delayed puberty and conditions of GnRH deficiency, few studies have examine...

Constitutional delay of growth and puberty (CDGP) is the most common diagnosis among males and females with pubertal delay, but it can be diagnosed only after exclusion of other underlying conditions. Most of the boys with delayed puberty have CDGP, but about 5–10% have hypergonadotropic hypogonadism (including Klinefelter), 10% have permanent hypogonadotropic hypogonadism (including Kallmann syndrome and idiopathic hypogonadotropic hypogonadism), and 10% have a transient...

GnRH neurons are vital for reproductive competence. These neurons originate mainly in the nasal epithelium and migrate to the preoptic region of the hypothalamus during foetal development. Defective migration may result in Hypogonadotropic Hypogonadism (HH), a condition in which puberty is never or only partially achieved.Little is known about the molecular ontogeny and regulation of GnRH neurons. Their anatomical localisation and small numbers (about 10...

Puberty is a fascinating transition period in the mammalian lifespan, but the biological control of pubertal timing remains poorly understood. Developmental abnormalities of the gonadotropin-releasing hormone (GnRH) neuronal network have been shown to be responsible for disorders of pubertal timing, in a spectrum of conditions ranging from idiopathic hypogonadotropic hypogonadism (IHH) to self-limited delayed puberty. We hypothesized that important regulators of pubertal timin...

Background: Both undernutrition and chronic inflammation impair linear growth through resistance to GH. Fibroblast growth factor 21 (FGF21) is known as an important regulator of the metabolic adaptation to fasting. Elevated expression of FGF21, secondary to prolonged undernutrition has been identified to develop GH resistance and subsequent attenuation of skeletal growth and growth plate chondrogenesis in both mice and human. However, the mechanism of FGF21’s actions rema...

Background: Fibroblast growth factor 21 (FGF21) is a key metabolic regulator in the adaptation to fasting. In food-restricted mice, inhibition of skeletal growth appears to be mediated by the antagonistic effect of FGF21 on GH action in the liver and in the growth plate (Kubicky et al. 2012, Yu et al. 2012). The role of FGF21 in growth regulation in humans is currently unknown.Objective and hypothesis: To provide mechanistic insights in...

Background: Childhood growth is an indicator of health/well-being. Growth monitoring identifies treatable conditions in apparently healthy children and prevents inappropriate referrals. Systematic growth monitoring is not currently a UK priority and growth disorders are frequently diagnosed late.Objective: Develop and test the accuracy of GrowthMonitor, an app which enables families to measure a child’s height at home as a cost-effective alternative...

Objectives: Abnormal pubertal timing affects >4% of adolescents and is associated with adverse health outcomes. Up to 80% of variation in the timing of pubertal onset is genetically determined. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern, but in the majority the neuroendocrine pathophysiology and genetic regulation remain unclear. Mis-regulation of the embryonic migration of GnRH neurons has been implicated in the pathogenesis of DP (Howar...

Hypogonadotropic hypogonadism (HH) is a rare reproductive disorder that results in a lack of normal pubertal development and reduced potential for fertility in adult life. The condition is characterised by low circulating sex steroid concentrations resulting from a deficiency of pituitary gonadotropin production. HH may be congenital or acquired, most commonly due to tumour or treatment for malignant disease. When associated with anosmia it is termed Kallmann syndrome. HH is a...

Background: Delta-like homologue 1 (DLK1) encodes a transmembrane protein, which may also be secreted into the circulation. Levels are known to rise in maternal serum during late gestation and our genetic studies in the mouse have shown that this DLK1 arises from the conceptus. The cell population that secretes DLK1 into the maternal circulation has not been identified. In humans DLK1 has been shown to be differentially expressed in intrauterine growth restricted (IUGR) when c...