Steroid hormones modulate expression of cytochrome P450 enzymes in male hamster reproductive tract and leiomyosarcomas

Syrian hamsters treated with estrogen and androgen for 8 months develop lei omyosarcomas in the vas deferens, Metabolism of estrogen by cytochrome P450 s (CYPs) produces catechols and reactive oxygen species, and may contribute to tumor formation. To examine this issue, male hamsters were treated with 17 beta -estradiol (E2), testosterone propionate (TP) or both hormones. Re productive tract tissues from control and treated animals were immunostaine d with antibodies specific for four CYP enzymes (1A1, 1A2, 1B1 and 3A1/2). Immunoreactive CYP1A1 was not found in the reproductive tract of control or treated animals. In untreated hamsters, CYP1A2 was detected only in princi pal cells of the caput epididymis. TP alone had no effect, but treatment wi th E2 induced expression of CYP1A2 in columnar epithelial cells throughout the epididymis and lining of the vas deferens. Treatment with E2 + TP block ed the induction of CYP1A2 seen in surface epithelial cells treated with E2 alone, but not the constitutive expression of this enzyme. Instead, simult aneous exposure to both hormones induced CYP1A2 in basal cells of the epidi dymis and vas deferens, CYP3A1/2 was not detected in the reproductive tract of control or TP-treated males, but immunostaining was induced in the inne r layer of vas deferens smooth muscle by E2, and in all smooth muscle layer s by dual hormone treatment. In controls, CYP1B1 was present in smooth musc le lining the epididymis and surrounding the vas deferens and dual hormone treatment increased staining intensity for CYP1B1 in these cells. Immunorea ctive CYP1A2 was not detectable in leiomyosarcomas but the enzyme was prese nt in both columnar and basal cells of the vas deferens epithelium adjacent to the tumors. In contrast, tumor cells showed heterogeneous expression of both CYP1B1 and CYP3A1/2. The relationships between hormone treatment, dif ferential CYP expression and tumor formation strengthen our hypothesis that metabolism of estrogen is an important element in this model of hormonal c arcinogenesis.