Effects of estradiol, progestogens, and of tibolone on breast proliferation and apoptosis

Abstract

Aim To study the effects of estrogen therapy, alone or combined with progestogens, and of tibolone on the expression of proliferation and apoptosis markers in normal breast tissue.

Methods Thirty 250-day-old Wistar rats were castrated and 3 weeks later received one of the following treatments by gavage for 5 weeks: (1) estradiol benzoate; (2) estradiol benzoate + medroxyprogesterone acetate; (3) estradiol benzoate + norethisterone acetate; (4) estradiol benzoate + dydrogesterone; (5) tibolone; (6) placebo. Following treatment, the expression of proliferating cell nuclear antigen (PCNA) and caspase-3 was analyzed by quantitative immunohistochemistry in the breast tissue, and proliferation and apoptosis were analyzed semiquantitatively by microscopic imaging.

Results There was a statistically significant difference among the groups for PCNA, caspase-3 and the caspase-3 : PCNA ratio. Tibolone was associated with the lowest proliferative activity, followed by estradiol benzoate + dydrogesterone; however, estradiol benzoate + dydrogesterone showed the greatest rate of apoptosis.

Conclusions The various progestogens can have more or less proliferative and pro-apoptotic effects than estradiol alone. Among the treatment schemes analyzed, the estradiol + dydrogesterone combination resulted in a higher apoptosis rate in relation to the proliferation rate and tibolone was associated with the lowest proliferation.

Key words::

• PROLIFERATION
• APOPTOSIS
• ESTROGEN
• PROGESTOGENS
• BREAST CANCER

Conflict of interest Luciano M. Pompei is lecturer for the following pharmaceutical companies: Abbott, Bayer, GSK, MSD, Libbs, and TEVA. Cesar Eduardo Fernandes is lecturer for the following pharmaceutical companies: Bayer, Sanofi and TEVA. The other authors have no conflict of interest to declare.

Source of funding This research was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) – Process # 2011/13704-0.