CC BY 4.0 · Rev Bras Ginecol Obstet 2019; 41(12): 703-709
DOI: 10.1055/s-0039-3399552
Original Article
Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

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

Efeito da testosterona em marcadores de proliferação e apoptose em mamas de ratas ovariectomizadas
Jussara Celi Conceição Oliveira
1   Faculdade de Medicina do ABC, Fundação do ABC, Santo André, São Paulo, Brazil
Marcelo Luis Steiner
2   Department of Gynecology and Obstetrics, Faculdade de Medicina do ABC, Santo André, SP, Brazil
Thérèse Rachell Theodoro
3   Department of Biochemistry, Faculdade de Medicina do ABC, Santo André, SP, Brazil
Ana Maria Amaral Antonio Mader
4   Department of Pathology, Faculdade de Medicina do ABC, Santo André, SP, Brazil
Giuliana Petri
5   Biottery Coordination, Faculdade de Medicina do ABC, Santo André, SP, Brazil
Luiz Carlos Abreu
6   Outline and Scientific Writing Laboratory, Faculdade de Medicina do ABC, Santo André, SP, Brazil
Maria Aparecida da Silva Pinhal
3   Department of Biochemistry, Faculdade de Medicina do ABC, Santo André, SP, Brazil
César Eduardo Fernandes
2   Department of Gynecology and Obstetrics, Faculdade de Medicina do ABC, Santo André, SP, Brazil
2   Department of Gynecology and Obstetrics, Faculdade de Medicina do ABC, Santo André, SP, Brazil
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12. August 2019

02. Oktober 2019

19. Dezember 2019 (online)


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.

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