Effect of Testosterone on Proliferation Markers and Apoptosis in Breasts of Ovariectomized Rats

• Published in: Revista Brasileira de ginecologia e obstetrícia Vol. 41; no. 12; pp. 703 - 709
• Main Authors: Oliveira, Jussara Celi Conceição, Steiner, Marcelo Luis, Theodoro, Thérèse Rachell, Mader, Ana Maria Amaral Antonio, Petri, Giuliana, Abreu, Luiz Carlos, Pinhal, Maria Aparecida da Silva, Fernandes, César Eduardo, Pompei, Luciano Melo
• Format: Journal Article
• Language: English; Portuguese
• Published: Rio de Janeiro, Brazil Thieme Revinter Publicações Ltda 01.12.2019; Federação Brasileira das Sociedades de Ginecologia e Obstetrícia
• Subjects: Animals; apoptosis; Apoptosis - drug effects; Biomarkers - analysis; breast; Breast - cytology; Breast - pathology; Calcinosis - pathology; Caspase 3 - analysis; Cell Proliferation - drug effects; Estradiol - analogs & derivatives; Estradiol - pharmacology; Female; OBSTETRICS & GYNECOLOGY; Original; Original Article; Ovariectomy; Proliferating Cell Nuclear Antigen - analysis; proliferation; Rats, Wistar; testosterone; Testosterone - pharmacology; testosterone; proliferation; proliferação; testosterona; apoptosis; apoptose; mama; breast; ovariectomy; ovariectomia
• ISSN: 0100-7203; 1806-9339; 1806-9339
• DOI: 10.1055/s-0039-3399552

Abstract Objective  To investigate the action of testosterone (T), isolated or associated with estradiol benzoate (EB), on the proliferation markers and apoptosis of breasts of ovariectomized rats. Methods  A total of 48 castrated female Wistar rats were divided into 6 groups, and each of them were submitted to one of the following treatments for 5 weeks: 1) control; 2) EB 50 mcg/day  + T 50 mcg/day; 3) T 50mcg/day; 4) EB 50 mcg + T 300 mcg/day; 5) T 300 mcg/day; and 6) EB 50 mcg/day. After the treatment, the mammary tissue was submitted to a histological analysis and immunoexpression evaluation of proliferation markers (proliferating cell nuclear antigen, PCNA) and apoptosis (caspase-3). Results  There was a statistically significant difference among the groups regarding microcalcifications and secretory activity, with higher prevalence in the groups treated with EB. There was no difference among the groups regarding atrophy, but a higher prevalence of atrophy was found in the groups that received T versus those that received EB + T. There was a difference among the groups regarding the PCNA ( p  = 0.028), with higher expression in the group submitted to EB + T 300 mcg/day. Regarding caspase-3, there was no difference among the groups; however, in the group submitted to EB + T 300 mcg/day, the expression was higher than in the isolated T group. Conclusion  Isolated T did not have a proliferative effect on the mammary tissue, contrary to EB. Testosterone in combination with EB may or may not decrease the proliferation, depending on the dose of T.