Regulation of epidermal growth factor receptor by androgens in human endometrial cells in culture

Women with polycystic ovaries (PCO) have a thicker endometrium than women w ith normal ovaries. This cannot be due to unopposed oestrogen, as it occurs in ovulatory cycles. Androgens may be involved, as these are raised in wom en with PCO, The effects of steroids are partly mediated by growth factors and their receptors, The aim of this study was to investigate the effect of androgens on epidermal growth factor (EGF) receptor in human endometrium, Endometrium was enzymatically dispersed and glands and stromal cells separa ted. Cells were incubated in Ham's F10 medium supplemented with 5% charcoal -stripped fetal calf serum and either androgens or vehicle. Specific bindin g of [I-125]labelled EGF was measured. Testosterone and dihydrotestosterone (DHT) (10 mu mol/l) increased EGF receptor concentration (control 100 +/- 9%, testosterone 196 +/- 23% control; control 100 +/- 1%, DHT 244 +/- 6% co ntrol) but did not alter receptor affinity. The effect of testosterone was inhibited by the anti-androgen hydroxyflutamide, but not by the antioestrog en ICI182780 nor the aromatase inhibitor 4-hydroxyandrostenedione. EGF rece ptor levels were increased by androstenediol (control 100 +/- 2%, androsten ediol 120 +/- 10% control) but not by androstanediol, dehydroepiandrosteron e (DHA), DHA sulphate or androstenedione, Testosterone and DHT increased EG F receptor concentrations in glandular epithelium (control 100 +/- 24%,test osterone 147 +/- 5%, DHT 185 +/- 30% control). These data suggest that andr ogens may have an effect on the endometrium via an increase in EGF receptor concentrations.