cells when oestrogen receptors are blocked by oestradiol

Summary Adrenal androgens show a dual and apparently opposite effect on the growth of oestrogen-responsive breast cancer: they stimulate growth on their own, but counteract the growth-stimulatory effect of oestrogens. Focusing on the inhibitory action we have studied the effects of 5-en-androstene-3p,17p-diol (ADIOL) on the growth of oestrogen-responsive MCF-7 breast cancer cells in the presence of oestrogens (oestradiol and diethylstilboestrol), antiestrogens (tamoxifen) and antiandrogens (hydroxyflutamide). The inhibition of oestrogen-stimulated growth, attained with nanomolar concentrations of ADIOL, was not modified by increasing concentrations of diethylstilboestrol up to 100 nm. This inhibition was counteracted by antiandrogens, which were unable to block the ADIOL stimulatory effect in steroid-free medium. On the other hand, in the presence of tamoxifen ADIOL showed an additive antiproliferative activity also in steroid-free medium, rather than the usual stimulatory effect. These results suggest that ADIOL stimulates breast cancer cell growth via oestrogen receptors, but inhibits oestrogen-stimulated growth via androgen receptors. Adrenal androgens, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS) and 5-en-androstene-3p,17p-diol (ADIOL), are the major secretory products of the adrenal gland. However, their physiological role is still unknown. Epidemiological and experimental studies suggest that they might affect the growth of human breast tumours (Bulbrook et al., 1971; Wang et al., 1975; Segaloff et al., 1980; Zumoff et al., 1981; Helzlsouer et al., 1992). In vitro studies showed that they may exert a dual and opposite effect on the growth of breast cancer cells (Adams e