Searchable abstracts of presentations at key conferences in endocrinology

ea0019p283 | Reproduction | SFEBES2009

Metabolic effects of insulin and modification by androgen in immortalised mouse granulosa cells

Joharatnam J , Hardy K , Franks S

Polycystic ovary syndrome (PCOS) is characterised by hyperandrogenism and insulin resistance. It is thought that androgen excess contributes to the mechanism of insulin resistance. Granulosa cells in PCOS demonstrate impaired insulin-induced glucose uptake and lactate accumulation1. The aim of this study was to characterise insulin signalling (via the PI3-Kinase (PI3-K) pathway) and glucose metabolism in an immortalised mouse granulosa cell line (KK1)2, a...

ea0003p230 | Reproduction | BES2002

FSH alters metabolism and increases chromosomal abnormalities in mouse cumulus-oocyte-complexes matured in vitro

Roberts R , Iatropoulou A , Franks S , Hardy K

In vitro maturation (IVM) of oocytes obtained from medium sized antral follicles could avoid the need for superovulation for in vitro fertilisation. FSH is routinely added to culture media during IVM but the effects on oocyte health are unclear. The aim of this study was to assess the effect of FSH on 1) the metabolic activity of individual mouse cumulus-oocyte-complexes (COCs) matured in vitro,and 2) the genesis of chromosomal abnormalities. 274 mouse COC...

ea0019oc36 | Thyroid, reproduction and endocrine tumours | SFEBES2009

Spatio-temporal expression of bone morphogenetic protein (BMP) antagonists during early follicle development

Fenwick M , Franks S , Stark J , Hardy K

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–...

ea0019p285 | Reproduction | SFEBES2009

Evidence for discordant granulosa cell proliferation in ovaries of prenatally androgenised sheep: a model for polycystic ovary syndrome

Comim F , Stubbs S , Hardy K , Franks S

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...

ea0009oc15 | Oral Communication 2: Reproduction and growth | BES2005

Early preantral follicle development in polycystic ovaries (PCO) differs according to ovulatory status

Franks S , Stubbs S , Webber L , Hardy K

Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility; anovulation in PCOS is characterised by arrest of antral follicle growth that may reflect the abnormal endocrine environment. However, it has recently been shown that preantral follicle development is also abnormal in PCO (Webber et al, Lancet 2003, 362 1017). In that study, the proportion of follicles in the primordial, resting, phase, was reduced, compared to normal ovaries, in tissue from bo...

ea0004p74 | Reproduction | SFE2002

Localisation of type I IGF receptor and androgen receptor proeins in small preantral follicles of human ovaries

Webber L , Birch R , Flanagan A , Hardy K , Franks S

Little is known about the place of insulin-like growth factors (IGFs) in preantral follicle development, although there is considerable evidence that IGFs are important in antral folliculogenesis. In the rat, isolated large preantral follicles developed better when cultured in vitro in the presence of IGF-I than without (Zhao et al 2001). In the same study, reverse transcriptase polymerase chain reaction identified mRNA for IGF-I and the type I receptor in the granulosa/theca ...

ea0003p229 | Reproduction | BES2002

Expression of mRNA for IGF-1, IGF-2, type 1-IGF receptor, type 2-IGF receptor and insulin receptor in isolated, human preantral follicles

Rice S , Taylor D , Margara R , Franks S , Hardy K

The role of the intra-ovarian insulin-like growth factor (IGF) system in preantral follicle development is unclear. Here we have examined the expression of mRNA for insulin-like growth factor-1 (IGF-1), IGF-2, Type 1-IGF receptor, Type 2-IGF receptor and insulin receptor (IR) in human pre-antral follicles at different stages. Ovarian cortex biopsies (5mm3) were obtained (with informed consent) during gynaecological surgery from six women (age 32.2 plus/minus SD 2.2,...

ea0002p74 | Reproduction | SFE2001

Morphological differences in preantral follicle distribution between normal and androgenised ovine ovaries

Birch R , Robinson J , Hardy K , Franks S

Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility in women, but its aetiology is poorly understood. There is evidence for a primary disorder of androgen secretion, which has its origins before puberty, but it is not clear how this may cause the characteristic ovarian abnormalities. We have developed an ovine model for PCOS to explore possible differences between the small preantral follicles of androgenised female lambs with those of normal ova...

ea0011p27 | Bone | ECE2006

Synergistic induction of osteoblastic local glucocorticoid metabolism by inflammatory cytokines and glucocorticoids: a novel mechanism for glucocorticoid-induced bone disease

Kaur K , Hardy R , Stewart PM , Rabbitt EH , Hewison M , Cooper MS

When used to treat inflammatory disease therapeutic glucocorticoids (GCs) cause rapid bone loss. However clinical studies suggest that in patients without inflammation GCs have little impact on the skeleton. The mechanism by which inflammation magnifies the effects of GCs is unknown. We have proposed that intracellular GC generation (inactive cortisone/prednisone to active cortisol/prednisolone conversion) via the 11 beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) enzyme d...

ea0009p42 | Growth and development | BES2005

Hyperinsulinaemia and insulin resistance in an animal model of Polycystic Ovary Syndrome (PCOS)

Robinson J , Chambers G , Shah A , Hardy K , Franks S , Evans N

PCOS is the most common endocrine disorder of premenopausal women. The in utero testosterone-treated ewe shares several key features with PCOS women (sub/infertility, multi-follicular ovaries, hypersecretion of gondotrophins and androgens) and, therefore, may be a useful animal model for this condition. In addition to reproductive abnormalities, PCOS women are at increased risk of hyperinsulinaemia and insulin resistance. The aim of this study was to determine if similar metab...