Action of metformin on the insulin-signaling pathway and on glucose transport in human granulosa cells.

Context: Hyperinsulinemia in polycystic ovary syndrome is widely treated with the insulin sensitizer metformin, which, in addition to its systemic effects, directly affects the ovarian insulin-stimulated steroidogenesis pathway.

Objective: Our aim was to investigate the interaction of metformin with the other insulin-stimulated ovarian pathway, namely that leading to glucose uptake.

Design: Human granulosa-luteal cells were cultured with metformin (10(-7) M), insulin (10 ng/ml) or metformin and insulin (met + ins) combined.

Evidence that low-dose, long-term genistein treatment inhibits oestradiol-stimulated growth in MCF-7 cells by down-regulation of the PI3-kinase/Akt signalling pathway.

The reduced incidence of breast cancer in certain Eastern countries has been attributed to high soy diets although this evidence is simply epidemiological. One of the major constituents of soy is genistein, but paradoxically this phytoestrogen binds to oestrogen receptors and stimulates growth at concentrations that would be achieved by a high soy diet, but inhibits growth at high experimental concentrations. To determine the effects of low-dose, long-term genistein exposure we have cultured MCF-7 breast cancer cells in 10 nM genistein for 10-12 weeks and investigated whether or not this long-term genistein treatment (LTGT) altered the expression of oestrogen receptor alpha (ERalpha) and the activity of the PI3-K/Akt signalling pathway.