Effects of dehydroepiandrosterone and other sex steroid hormones on mammary carcinogenesis by direct injection of 7,12-dimethylbenz(a) anthracene (DMBA) in hyperprolactinemic female rats.

The present study was performed to investigate the effects of dehydroepiandrosterone (DHEA) compared with those of sex steroid hormones on the mammary tumor induced by local injection of 7,12-dimethylbenz(a) anthracene (DMBA) in hyperprolactinemic female rats. Under sustained hyperprolactinemia induced by pimozide (PMZ) from day 21, DMBA was injected locally into the mammary glandular tissues on day 73. Rats were divided into 5 groups as follows; steroid free (DP group), 17 beta-estradiol (DP + E2 group), testosterone (DP + T group), progesterone (DP + Prog group), or dehydroepiandrosterone (DP + DHA group). The growth pattern and histological classification of the tumor in these 5 groups and rats treated only with DMBA (D group) were examined. All of the tumors grew to a size of 10 mm in diameter and after retaining the size for a certain duration, increased the size rapidly again (onset of rapid tumor growth). The period from the day of DMBA administration to that of onset of the rapid tumor growth in DP group was shorter than in D group, and the period in DP + DHA was longer than DP group and longest in steroid-treated groups. The incidence of adenocarcinoma was 2 tumors/16 animals in D group, 9/11 in DP group, 5/11 in DP + Prog group, 2/7 in DP + E2 group, 2/8 in DP + T group, and 0/10 in DP + DHA group. The incidence of adenocarcinoma in each steroid group except in DP + Prog group was lower than in DP group. These results suggest that prolactin (PRL) increases the incidence of adenocarcinoma in the DMBA-induced mammary tumor model, and DHEA especially decreases the incidence of adenocarcinoma.