Inhibition of Preovulatory Gonadotropin Secretion and Stimulation of Prolactin Secretion by 7,12-Dimethylbenz(a)anthracene in Sprague-Dawley Rats1

Serum luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone, and growth hormone and hypothalamic luliberin and thyroliberin contents were measured at given times of the estrous cycle in a dimethylbenz(a)anthracene (DMBA)-susceptible strain of rat (Sprague-Daw ley) and in a DMBA-resistant strain of rat (Wistar) for periods up to the appearance of the first mammary tumors in DMBAsusceptible animals. Tumors usually appeared with =100% incidence around the 14th to 15th estrous cycle after DMBA treatment in Sprague-Dawley rats. Hormonal determinations were done by using groups of 4day cycling rats of both strains which were given DMBA or the vehicle (sesame oil) on a single diestrus I at around 55 days of life. Animals were sacrificed by decapitation without previous anesthesia on the morning and afternoon of proestrus and estrus during the 5th and 11 th estrous cycles after treatment. In Sprague-Dawley female rats, DMBA significantly inhibited luteinizing hormone and follicle-stimulating hormone surges and stimulated the prolactin surge on the afternoon of proestrus at any estrous cycle after treatment (the timing of preovulatory surges was the same in both strains for any estrous cycle or treatment); no difference was found for any hormone at other times of the estrous cycle. In contrast, Wistar rats did not show deranged preovulatory or basal prolactin and gonadotropin release after treatment with the carcinogen; in addition, no difference was found for any other hormone at any time tested. These results show that there is a specific and transient hormonal deregulation in a DMBA-susceptive strain of rats. Inasmuch as the hormonal imbalance was essentially the same throughout the induction period, an early and persistent alter ation in centers implicated in the hormonal cyclicity of the hypothalamopituitary axis must result from DMBA treatment.