Endocrine Abstracts

Metformin is commonly used to treat insulin resistance in women with polycystic ovary syndrome (PCOS) and also has direct effects on the ovary. The mechanism of this action is unknown, but could be via insulin-independent pathways, namely AMP activated protein kinase (AMPK). AMPK is an energy sensor, activated when ATP levels are depleted causing an inhibition of anabolic and an activation of catabolic pathways. We hypothesised that in the ovary, metformin acts via</...

Based on the hypothesis that ‘incessant ovulation’ and ‘ovulation-related inflammation’ are associated with the development of epithelial ovarian cancer, we have investigated in vitro the role of androgen and progesterone pre-receptor metabolism and steroid receptor signalling in human ovarian surface epithelium (hOSE) wound healing. Ovulation-associated injury was mimicked with exposure of primary hOSE cells to interleukin-1α, whereas post-ovul...

Extracts of black cohosh (BCE) are frequently used as an alternative to conventional HRT to treat menopausal symptoms, particularly in Germany and the United States. In fact, BCE is the 14th most popular herbal product in the US and in 2003 sales were at least $15.7 million. Evidence for an increased incidence of breast cancer in long-term users of HRT has reduced its use and may increase the use of alternative treatments. These still require rigorous scientific investigation,...

AMH, the fetal testicular sexual differentiative factor, is now implicated in adult ovarian function. Antral follicle immunohistochemistry demonstrated AMH protein and message, the staining peaking around 4 mm. Interestingly, AMH-knockout mice have increased FSH sensitivity. Our aim was to measure AMH in follicular fluid and cell-conditioned medium and AMHRII in normal ovaries from women undergoing TAH/BSO.Follicles were dissected intact, follicular flui...

Recent evidence indicates that the increase in follicle numbers seen in PCOS occurs early in folliculogenesis, and that androgens are implicated in this. In primates and sheep, androgen excess in-utero results in ovarian changes similar to those in PCOS. We have recently shown using a novel in ovo model, that testosterone added to implanted human tissue increased primary follicles compared to untreated tissue (Qureshi et al. 2005). This is similar to the p...

BackgroundCurrent techniques to study the early stages of follicular development (i)in vitro(/i) are handicapped by the spontaneous wholesale transition of primordial to primary follicles and by primary follicle arrest. We have circumvented this problem by culturing fragments of ovarian cortical tissue on the chorioallantoic membrane (CAM) of chick embryos and shown it to be successful for the (i)in ovo(/i) culture of cortical slices from a variety of sp...

Current techniques to study (i)in vitro(/i) the early stages of follicular development are handicapped by the spontaneous wholesale transition of primordial to primary follicles. Implantation of ovarian tissue into SCID mice is possible but expensive. We have, therefore, adapted a model first described in 1958. Fragments of ovarian cortex are implanted on the chorioallantoic membrane (CAM) of 5-6 day old fertilised chick eggs. The membrane is rich in blood vessels and results ...

The capacity of the adrenal to produce cortisol is controlled in part by the transcription of 21 hydroxylase(CYP21) and production of androgens by 17 hydroxylase/17-20 lyase(CYP17) in response to secretogoues including ACTH, angiotensin-II(A-II) and forskolin. Both mRNA and protein expression of CYP21 was upregulated in the presence of forskolin and A-II alone and in combination in vitro H-295 adrenocortical cells, as detected by northern and western blotting. Whereas, ...

There is evidence from animal studies that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is essential for normal reproductive function. Vitamin D deficient rats have reduced fertility, and VDR null mutant mice demonstrate impaired folliculogenesis. We have recently demonstrated that 1,25(OH)2D3 suppressed the production of oestradiol (E2) independently of progesterone (P) in luteinised, but not in non-luteinised human granulosa cells, suggesting that 1,25(OH)<s...

At least 90% of human ovarian cancers may originate in the OSE. Most studies indicate that EOC is oestrogen responsive. Paradoxically, ovarian cancer generally occurs after the menopause, so the question arises if oestrogen is involved, where does it come from? We hypothesise that the high circulating concentrations of conjugated (inactive) oestrogens in post-menopausal women are substrates for formation of active oestrogen in the OSE through the hydrolytic enzyme activity of ...