The mechanism of action of epidermal growth factor and transforming growthfactor alpha on aromatase activity in granulosa cells from polycystic ovaries

We investigated aromatization and the mechanism of action of epidermal grow th factor (EGF) and transforming growth factor alpha (TGF alpha) on oestrad iol biosynthesis in freshly prepared granulosa cells from polycystic ovarie s. Freshly prepared granulosa cells from polycystic ovaries incubated for o nly 3 h under basal conditions secreted significantly (P < 0.001) greater a mounts of oestradiol-17 beta than that of granulosa cells from normal ovari es. 8-Bromo-cyclic adenosine monophosphate (8-Br-cAMP), but not follicle st imulating hormone (FSH) or luteinizing hormone (LH), further enhanced this activity. Both EGF and TGF alpha inhibited gonadotrophin or 8-Br-cAMP-stimu lated, but not basal, oestradiol production. LH receptor (LHR) binding, est imated by immunolabelling the bound LH, was significantly (P < 0.001) reduc ed in granulosa cells from polycystic ovaries when compared with cells from normal ovaries. EGF or TGF alpha significantly reduced the binding in cult ured cells from all patient groups (P < 0.05). More interestingly, a furthe r increase of the inhibitory effect was seen in granulosa cells from polycy stic ovaries (P < 0.001). In conclusion, granulosa cells from polycystic ov aries contain high levels of basal aromatase activity in vitro, which is pr obably inherited from the in-vivo condition. EGF and TGF alpha suppress oes tradiol synthesis at a step beyond the production of cAMP and also LHR bind ing with more effect in granulosa cells from polycystic ovaries.