In vitro estrogen-like effects of 7,12-dimethylbenz(a)anthracene on anterior pituitary dopamine receptors of rats.
The ability of 7,12-dimethylbenz(a)anthracene (DMBA), a potent inducer of mammary tumors, to mimic short term effects of estradiol (17 beta-E2) on the anterior pituitary, was tested in vitro. Incubation of anterior pituitaries from ovariectomized rats with DMBA resulted in a marked depletion of membrane dopamine receptors (labeled with [3H] spiperone) and a parallel stimulation of prolactin (PRL) release. Maximal receptor depletion and PRL release were obtained after 15-30 min of incubation with 10(-8) M DMBA. These effects were reversible and already significant after a 5-min incubation. Their magnitude, dose dependency, and time course were identical to those reported for 17 beta-E2. A structurally related noncarcinogenic polycyclic aromatic hydrocarbon, phenanthrene, had no effect on [3H]spiperone binding or PRL release. When DMBA and 17 beta-E2, at suboptimal concentrations, were simultaneously added to the culture medium, no synergistic effect could be observed. When 10(-8) M of both compounds were introduced simultaneously, the decrease in dopamine receptors and the increase in PRL release were not greater than those observed in the presence of 10(-8) M of only one compound, indicating that the same mechanism(s) can be involved. These data suggest that DMBA in desensitizing lactotrophs to dopamine and in releasing PRL, by direct estrogen-like actions on anterior pituitary, may provide a hormonal state conducive to tumor development.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D010616:Phenanthrenes / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism
D010616:Phenanthrenes; D011954:Receptors, Dopamine; C031181:phenanthrene; D004958:Estradiol; D013134:Spiperone; D015127:9,10-Dimethyl-1,2-benzanthracene; D011388:Prolactin