Endocrine Abstracts

C-type natriuretic peptide (CNP) is the ancestral and most highly conserved member of the mammalian natriuretic peptide family. Although broadly expressed throughout the periphery (bone, gonads, kidneys), CNP is the major natriuretic peptide of the brain and CNS and is suspected to influence neuroendocrine function. Our recent studies using fetal human pituitary samples has shown that the gene encoding CNP, NPPC, is expressed early on in pituitary development but a co...

Glucocorticoid signalling is essential for cardiac maturation late gestation. In mice, global glucocorticoid receptor deficiency (GR−/−) severely impairs cardiac function and ultrastructure at embryonic day (E) 17.5. To dissect direct effects of GR deficiency in the heart from effects on other systems, Sm22α-Cre mice were crossed with ‘floxed’ GR mice to generate SMGRKO mice with disrupted GR signalling in cardiomyocytes and vascular smoot...

Introduction: Epidemiological evidence suggests that a poor diet during pregnancy leads to offspring with higher risk of chronic diseases in adulthood. Our previous work in sheep showed that mild protein-energy malnutrition in early gestation results in decreased insulin signalling in the liver, and changes in vascular endothelial growth factor (VEGF) in the kidney. The current study explored whether these changes are generalised phenomena, or organ-specific.<p class="abst...

Background: One in five women is obese at antenatal booking. Maternal obesity increases risk of offspring complications including higher birthweight. We hypothesised that this is mediated by altered action of maternal glucocorticoids, key regulators of fetal growth and development. We compared cortisol levels during pregnancy and placental glucocorticoid sensitivity in obese and lean women.Methods: With ethical approval serum cortisol levels were measure...

The hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by germline mutations of the dual zinc-finger (ZnF) transcription factor, GATA3. To date, 51 GATA3 mutations have been reported, which can be divided broadly into three structural-functional classes: i) mutations that lead to a loss of DNA binding and involve ZnF2; ii) mutations, usually of ZnF1, that bind DNA but result in reduced DNA binding affinity; and iii) mut...

Background: Pubertal timing has importance both for the individual, but also for public health. Previous studies estimate that 60–80% of variation in pubertal onset is genetically determined. Recently, a large genome-wide association study (GWAS) meta-analysis identified 42 loci for age-at-menarche (AAM), which explained 3.6–6.1% of the variation in the general population, but causal genes have not been identified.CDGP is defined as pubertal on...

Introduction: We recently reported cases of segmental overgrowth due to mosaic heterozygous activating mutations in the p110α catalytic subunit of PI3K. The index case presented with life-long, massive overgrowth of both legs with a lean upper body. Mobility was threatened by continued growth. mTORC1 inhibition has been effective at slowing excess growth due to loss of PTEN function, a negative regulator of PI3K. We hypothesised that mTORC1 inhibition would also be effect...

Atrazine (ATR) is a widely used herbicide, with known effects as an endocrine disrupting chemical. Several studies have implicated ATR in causing disorders of sex development in reptiles, and chronic exposure can cause an increase incidence of intersex in fish, suggesting that the hypothalamo-pituitary–gonadal axis is a major site of ATR action. In this study, we investigated whether acute exposure (hours to days) to ATR could cause abnormalities in the development of Zeb...

Background: Improved knowledge of the range of anomalies encountered in DSD may improve our understanding of the underlying aetiology. However, given the rarity of these conditions, thorough analysis of congenital anomalies in DSD has not previously been possible.Aims: To discover the frequency of congenital anomalies in DSD, and to identify patterns of anomalies within specific conditions.Methods: 1050 registered cases on The I-DS...