ESTROGEN-LIKE EFFECTS OF 7,12-DIMETHYLBENZ(A)ANTHRACENE ON THE FEMALE RAT HYPOTHALAMOPITUITARY AXIS

We have recently demonstrated that 7,12-dimethylbenz(a)anthracene (DMBA), a potent inducer of mammary tumors in rodents, can in vitro decrease the number of membrane dopamine D2 receptors and stimulate prolactin (PRL) release, by direct estrogen-like actions on anterior pituitary. In the present study, we tested the ability of DMBA to mimic the in vivo estradiol (17βE2) effects on pituitary D2 receptors and on PRL as well as LH release. We have found that DMBA, like 17βE2, when injected to ovariectomized rats, induced a decrease in the number of anterior pituitary D2 receptors, a release of PRL and exerted a biphasic (acute negative and longer term positive) action on LH secretion. We thus examined the ability of DMBA to interact with 17βE2 receptors in the hypothalamo-pituitary axis: DMBA binds to the pituitary cytosolic estrogen receptors with an affinity 0.001% that of 17βE2. Finally [3H]DMBA binds to hypothalamus-containing brain sections. This binding was displaced partially by RU 2858 a pure estrogen agonist and totally by tamoxifen, a purported estrogen antagonist. No competition for [3H]DMBA binding was observed with an androgen (RU 1881) or a glucocorticoid (RU 26988) agonist. From these data, it may be concluded that DMBA can act as a partial estrogen in pituitary and hypothalamic tissues. © 1990.