Endocrine Abstracts

PCOS is associated with increased androgens, elevated insulin and obesity. As obesity and androgens promote insulin resistance and hyperinsulinemia increases ovarian androgen production, and the likelihood of obesity, the interaction between these factors is complex. We investigated the development of insulin resistance, hyperandrogenism and obesity using a clinically realistic ovine model of PCOS. Exposure of the pregnant ewe to increased testosterone from d62 to d102 of gest...

Introduction: The human endometrium has a remarkable capacity for repeated repair following the inflammation of menstruation. This occurs without scarring or loss of function but mechanisms involved remain undefined. Aberrations in endometrial repair may lead to pathology such as heavy menstrual bleeding (HMB). The transforming growth factor-β superfamily has been implicated in efficient wound repair and has a potential role in menstrual repair. Downstream of TGF-β, ...

Central obesity and increased visceral adipose tissue (VAT) are key factors contributing to metabolic dysfunction in PCOS. We therefore hypothesized that there would be alterations in the morphology and function of adipocytes from visceral fat depots. The female offspring of pregnant sheep treated biweekly with either 100 mg of testosterone propionate (TP) or vehicle control (C) from day 62–102 of gestation develop a clinically realistic PCOS-like condition. They develop ...

Women with Polycystic Ovary Syndrome (PCOS) are at increased risk of developing insulin resistance, obesity and dyslipidemia, however obesity per se does not explain the higher incidence of insulin resistance in PCOS women when compared to the general population. Altered adipose tissue morphology and function may be a central factor contributing to metabolic disturbances in PCOS. Using a clinically realistic ovine model of PCOS we reported hyperinsulinaemia and early ...

Exposure of pregnant sheep to increased concentrations of testosterone during midgestation results in a PCOS-like condition in the female offspring that includes increased hepatic IGF1. The aim of this study was to investigate the molecular pathophysiology of this increase. We studied 11-month-old female offspring whose mother had been treated with testosterone propionate (TP: 100 mg) in oil (n=8), or oil control (n=4) twice weekly from day 62 to 102 gestatio...

Background: The potential for a healthy life is programmed by in utero development. Fetal development is impacted by perturbed hormonal signalling, with lifelong consequences. Polycystic Ovary Syndrome (PCOS), affecting over 10% of women, is an important condition linked to an altered prenatal endocrine environment. Women with PCOS have increased androgen concentrations, including during pregnancy. Increased prenatal androgen exposure is associated with a PCOS-phenoty...

Within target cells, cortisol-cortisone inter-conversion is catalysed by both a NADP(H)-dependent, bidirectional type 1 11β-hydroxysteroid dehydrogenase (11βHSD1) enzyme and by a NAD+-dependent, unidirectional type 2 11βHSD (11βHSD2) isoenzyme. Since several published studies have reported altered glucocorticoid metabolism in polycystic ovary syndrome (PCOS), the current study assessed whether prenatal exposure of lambs to testosterone propionate...

Introduction: Adult male offspring of women with PCOS have increased dyslipidaemia, characterised by elevated triglycerides (TG), increased total and LDL-cholesterol (LDL-C), and hyperinsulinaemia. As altered intrauterine endocrine environments can ‘programme’ adverse health outcomes in adulthood we hypothesised that this dyslipidaemia was a consequence of a hyperandrogenic intrauterine environment. We used an outbred large animal model to identify if prenatal androg...

Introduction: Altered intrauterine endocrine environments can ‘programme’ adverse health outcomes. Linkage between altered androgen exposure in utero and adverse offspring health is robust. For example, increased maternal androgen concentrations and PCOS in female offspring and dyslipidaemia in male offspring. We hypothesised that the liver was a major target for androgenic programming in utero and hepatic dysfunction would be present in offspring. ...