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

Rev Bras Ginecol Obstet. 2019 Dec;41(12):703-709. doi: 10.1055/s-0039-3399552. Epub 2019 Dec 19.

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.

Objetivo: Investigar a ação da testosterona (T) isolada ou associada ao benzoato de estradiol (EB) na proliferação e apoptose de mamas de ratas ovariectomizadas. MéTODOS: Um total de 48 ratas Wistar castradas foram divididas em 6 grupos, e cada um foi submetido a um dos seguintes tratamentos durante 5 semanas: 1) controle; 2) BE 50 mcg/dia + T 50 mcg/dia; 3) T 50 mcg/dia; 4) BE 50 mcg + T 300 mcg/dia; e) T 300 mcg/dia; e f) BE 50 mcg/dia. Após o tratamento, o tecido mamário foi submetido a análise histológica e avaliação de imunoexpressão de marcadores de proliferação (antígeno nuclear de células proliferantes, PCNA) e apoptose (caspase-3).

Resultados: Houve diferença estatisticamente significante entre os grupos com relação às microcalcificações e à atividade secretora, com maior prevalência nos grupos tratados com BE. Não houve diferença entre os grupos quanto à atrofia, mas houve maior prevalência de atrofia nos grupos que receberam T versus os que receberam BE + T. Houve diferença entre os grupos quanto ao ANCP (p = 0,028), com maior expressão no grupo BE + T 300 mcg/dia. Com relação à caspase-3, não houve diferença entre os grupos, mas, no grupo BE + T 300 mcg/dia, a expressão foi maior do que no grupo de T isolada. CONCLUSãO: A T isolada não apresentou efeito proliferativo do tecido mamário, contrariamente ao EB. A T em associação ao EB pode diminuir ou não a proliferação, a depender da dose de T.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Biomarkers / analysis
  • Breast / cytology*
  • Breast / pathology
  • Calcinosis / pathology
  • Caspase 3 / analysis
  • Cell Proliferation / drug effects*
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Female
  • Ovariectomy
  • Proliferating Cell Nuclear Antigen / analysis
  • Rats, Wistar
  • Testosterone / pharmacology*

Substances

  • Biomarkers
  • Proliferating Cell Nuclear Antigen
  • estradiol 3-benzoate
  • Testosterone
  • Estradiol
  • Casp3 protein, rat
  • Caspase 3