Phytoestrogens act as estrogen agonists in an estrogen-responsive pituitary cell line

There is renewed interest in the medicinal value of natural plant products. One group of plant compounds, the phytoestrogens (PE), has been given considerable attention due to their ability to decrease the incidence of certain estrogen-dependent cancers. In this study, we evaluate the effects of PE on estrogen-dependent pituitary tumor cells by using the immortalized pituitary cell line PR1. Several PE were found to be active in PR1 cells, in that they bound to the estrogen receptor (ER), stimulated growth of PR1 cells, and induced an estrogenic response, prolactin secretion. The PE genistein, coumestrol, and zearalenone bound to the ER present in PR1 cells with an affinity 100-times lower than that of estradiol. However, resveratrol, a plant antitumor agent found in grapes, showed no significant binding to the ER. Zearalenone, coumestrol, and genistein were found to induce prolactin secretion and to stimulate growth, whereas resveratrol showed prolactin secretion but no growth stimulation. The estrogenic effects of PE in PR1 cells were ER dependent, in that addition of the antiestrogen ICI-182,780 inhibited prolactin response. Although resveratrol did not bind to the ER or stimulate growth, it induced prolactin secretion in both a dose- and time-dependent manner. The data presented here demonstrate that PE are active in lactotroph cells of the pituitary.