Endocrine Abstracts

Background: Maternal obesity during pregnancy is associated with adverse effects on fetal growth and development. As the placenta is a key organ regulating fetal growth, we hypothesized that maternal obesity is associated with altered placental expression and DNA methylation of genes regulating fetal growth and glucocorticoid metabolism and aimed to investigate this in first trimester (F; <12 weeks gestation) and term (T;>37 weeks gestation) placental tissues.<p cl...

Introduction: During gestation diminished maternal insulin sensitivity (IS) increases the availability of fuels allowing fetal growth. Very severe obesity (Class III obesity (OB), BMI≥40 kg/m2) is associated with reduced IS but it is 28 how nutrient availability differs and how this impacts on birth weight versus normal pregnancies (CON). Methods: 213 OB (median (interquartile range) 43.2(41.1–46.3) kg/m2) and 87 CON (BM...

Background: Testosterone deficiency is common in obesity and in type 2 diabetes mellitus. It is hypothesised that the expanded adipose pool, which is the major source of aromatase in men, depletes testosterone levels by excess conversion to estradiol. Individuals with either the GG rs2470152 polymorphism in intron 1 or a high number of TTTA repeats in intron 4 of CYP19 are known to have greater aromatase activity with demonstrable effects upon plasma estradiol and osteoporosis...

Background: Kisspeptin is a neuropeptide central to the regulation of gonadotrophin secretion but recent studies have suggested more diverse roles in human physiology. Kisspeptin is a potent inhibitor of tumour metastasis and plays a role in placentation, both processes involving angiogenesis. In addition, Kisspeptin and its receptor, GPR54, have been identified in human blood vessels including aorta, coronary artery and umbilical vein, where they mediate vasoconstriction. We,...

Background: Aldosterone levels in plasma are reported to be associated with risk of hypertension. Aldosterone secretion from the zona glomerulosa is regulated acutely by the renin/angiotensin system and plasma potassium. The role of ACTH in regulation of aldosterone secretion is disputed.Aim: We have utilised a large population study of middle aged adults to test the extent to which acute aldosterone responses to ACTH are associated with cortisol respons...

The metabolism of glucocorticoids within adipose tissue, by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), is known to be altered in obesity and following high fat feeding. Until recently, little attention has been paid to the fat depots found directly adjacent to blood vessels. Emerging evidence suggests that perivascular adipose may play a key role in modulating vascular function. The presence of steroidogenic enzymes within perivascular adipose, and the eff...

Mifepristone (RU38486) is a progesterone and glucocorticoid receptor antagonist which is used clinically to induce medical abortion, and as a research tool, e.g., in metabolic syndrome and depression. We aimed to develop a sensitive method to detect and quantify mifepristone in human plasma.Analyses were developed using a Surveyor HPLC system, with a mobile phase of methanol:ammonium acetate (5 mM) (70:30; 0.4 ml/min) and a C18 column (5 μm; 2.1&#21...

There is evidence that an unbalanced maternal diet, combining a high ratio of protein to carbohydrate with low intakes of folate and green vegetables imposes a metabolic stress on the mother and fetus leading to fetal growth retardation. Because recent studies have shown that high protein maternal diets are associated with raised offspring blood pressure, we have assessed whether this form of unbalanced maternal nutrition is also associated with glucose intolerance.<p clas...

Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis in men of low birthweight may be an important link between early life events and adult metabolic syndrome. In animal models females are more sensitive to HPA axis programming by manipulations in utero, but whether gender influences susceptibility in humans is unknown.We studied 106 women aged 67-78 y, from Hertfordshire UK, in whom birthweight was recorded. None had pituitary or adrenal disease or were rec...

Urine 18-hydroxy cortisol ('18OHF') measurements are claimed to have the potential to discriminate between primary hyperaldosteronism due to either Conn's syndrome/adrenal adenoma (increased values) or idiopathic adrenal hyperplasia (normal values), and also to identify cases of glucocorticoid-suppressible hyperaldosteronism ('GSH').We have evaluated three urine 18-OHF methods using a panel of samples from patients with primary hyperaldosteronism [due to either adenoma (N=...