Interaction of estrogen receptors with drugs that affect prolactin secretion

The competition of bromocriptine and lisuride hydrogen maleate (LIM) with estradiol binding to various tissues was evaluated by the dextran coated charcoal method. Bromocriptine and LIM competitively inhibited the binding of [3H] estradiol to its cytosolic receptors in rat uterine, pituitary and hypothalamic tissue and in DMBA induced mammary tumors. Ki was 2 X 10(-5) M for bromocriptine and 2 X 10(-4) M for LIM. Metoclopramide, dopamine and L-dopa had no significant effect on [3H] estradiol binding. The interaction of bromocriptine and LIM was specific for estrogen receptors. There was no interaction with progesterone receptors from rat uterus and pituitary and with testosterone receptors from rat epididymis and testis. When tested for estrogenity in the immature rat uterus, bromocriptine and LIM induced specific estrogen inducible proteins such as cytosolic estrogen and progesterone receptors. However, they do not affect the uterine/body weight ratio and peroxidase activity. A clear interaction of inhibitors (bromocriptine and LIM) of prolactine secretion, with cytosolic estrogen receptors from various tissues was shown. Some in vivo estrogenic effect was also demonstrated in the immature rat uterine system.