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 theeffects of dehydroepiandrosterone (DHEA) compared with those ofsex steroid hormones on the mammary tumor inducedby local injection of 7, 12-dimethylbenz(a)anthracene (DMBA) inhyperprolactinemic female rats. Under sustained hyperprolactinemia induced bypimozide (PMZ) from day 21, DMBA was injectedlocally into the mammary glandular tissues on day73. Rats were divided into 5 groups asfollows; steroid free (DP group), 17 β-estradiol (DP+ E2 group), testosterone (DP + T group),progesterone (DP + Prog group), or dehydroepiandrosterone (DP+ DHA group). The growth pattern and histologicalclassification of the tumor in these 5 groupsand rats treated only with DMBA (D group)were examined. All of the tumors grew toa size of 10 mm in diameter andafter retaining the size for a certain duration,increased the size rapidly again (onset of rapidtumor growth). The period from the day ofDMBA administration to that of onset of therapid tumor growth in DP group was shorterthan in D group, and the period inDP + DHA was longer than DP groupand longest in steroid-treated groups. The incidence ofadenocarcinoma 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 0/10in DP + DHA group. The incidence ofadenocarcinoma in each steroid group except in DP+ Prog group was lower than in DPgroup. These results suggest that prolactin (PRL) increasesthe incidence of adenocarcinoma in the DMBA-induced mammarytumor model, and DHEA especially decreases the incidenceof adenocarcinoma. [ABSTRACT FROM AUTHOR]