Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. It is characterised by excessive ovarian androgen production which, in turn, has been implicated in the aetiology of aberrant follicular development. We have previously reported that prenatal exposure to androgens activates follicle growth1. It has been suggested that androgens may interact with the IGFs to promote the activation and growth of follicles. The aim of thi...

Objectives: To examine the effect on weight change of diet/lifestyle advice to maintain/achieve a healthy weight in an unselected PCOS population.Methods: All overweight patients attending the Reproductive Endocrine clinic with PCOS are routinely given lifestyle advice for weight loss by their consultant, offered referral to see a dietician and, when clinically appropriate, prescribed orlistat. Clinical notes were reviewed for 50 consecutive patients wit...

Polycystic ovary syndrome (PCOS) is associated with insulin resistance. Abnormally low glucose transporter 4 (GLUT4) expression has been shown in adipocytes from subjects with PCOS1 and skeletal muscle from type 2 diabetics2. Although GLUT4 expression is mostly restricted to classic insulin target tissues such as skeletal muscle, cardiac muscle and adipose, we have found it in granulosa cells (GCs) of mice3. Glucose uptake and metabolism by GCs...

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. It is characterized by hyperandrogenism, which results primarily from excess androgen production by ovarian theca cells (TCs). Obesity contributes to androgen excess in PCOS and previous studies in vitro using bovine TCs have shown that adiponectin (production of which is inhibited in PCOS) is a repressor of P450c17 activity. However, little is known about expression of adiponec...

Initial follicle growth results in a number of distinct morphological changes, such as cuboidalisation and proliferation of the granulosa cells (GC) as well as an increase in oocyte size.Cell adhesion molecules and intercellular junctions play a pivotal role in changes in cell shape. We hypothesize that change in GC shape is key, and that increased understanding of changes in cell adhesion and associated junctions will provide insight into the regulation...

In rodents and other mammals, it is well established that the production of certain TGF-β members including Gdf9 and Bmp15 by oocytes is important for follicle development to proceed. It is believed that these growth factors form part of a short loop paracrine system to regulate gene expression in neighbouring follicle cells. We propose that one aspect of this feedback loop may involve the genomic modulation of TGF-β antagonists in granulosa cells by oocyte-secreted ...

Polycystic ovary syndrome (PCOS) is characterised by reproductive, hyperandrogenic and dysmetabolic features (including insulin resistance). There remain major questions about the basis of the metabolic dysfunction in PCOS and about its genetic aetiology. Having genotyped samples from >460 PCOS cases and >1300 female controls, I recently successfully identified the first genome-sequence variant (the FTO gene) to be implicated in susceptibility to PCOS (Barber <i...

BMPs form part of the TGFβ superfamily, which are important regulators of proliferation and differentiation in many cell types. The intraovarian production of specific BMP members and their receptors in a stage-specific manner is crucial for normal follicle development to proceed. Regulation of BMP signalling pathways can occur by intracellular inhibition of the signal transducers (Smads), or by BMP antagonists that bind extracellular BMPs to prevent or alter ligand–...

Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility in women. Recent evidence suggests that early folliculogenesis is disordered and may contribute to development of anovulation in PCOS. Early follicle development in PCOS is characterised by increased expression of minichromosome maintenance protein-2 (MCM2), a marker of cell proliferation (Stubbs et al. 2007). Increased recruitment of growing preantral follicles has been reported in the p...

Recent studies have shown that serum concentrations of AMH (produced by granulosa cells of the human ovary) are positively related to the number of antral follicles and are negatively correlated with age. Like inhibin B (also a granulosa cell product) AMH is thought to be a useful clinical marker of follicle reserve. Serum AMH concentrations have been reported to be higher than normal in women with polycystic ovary syndrome (PCOS), which is characterised by an excess of antral...