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Doctoral Thesis
DOI
10.11606/T.10.2018.tde-31012018-120233
Document
Author
Full name
Maria Angélica Machado Arroyo
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Assís Neto, Antônio Chaves de (President)
Kfoury Junior, José Roberto
Oliveira, Moacir Franco de
Pereira, Flávia Thomaz Veréchia
Pereira, Ricardo José Garcia
Title in Portuguese
Efeito do letrozol no hipotálamo e gônadas de preás durante o desenvolvimento sexual
Keywords in Portuguese
Anabolizante
Aromatase
Displasia
Estrógenos
Infertilidade
Abstract in Portuguese
O letrozol é usado como terapêutico em desordens reprodutivas provocadas pelos altos níveis de estrógenos. A enzima citocromo P450 aromatase biossintetiza estrógenos a partir dos andrógenos em tecidos com capacidade esteroidogênica, como o cérebro, testículo e ovário. O objetivo do nosso estudo foi avaliar se o letrozol afeta o desenvolvimento das principais vias de controle reprodutivo de preás machos e fêmeas. Para tanto, consideramos o ganho de peso corporal, do testículo, do ovário e do cérebro, a progressão morfológica da espermatogênese e da foliculogênese, bem como a atividade enzimática da citocromo P450 aromatase nesses tecidos, comparado-os entre os grupos experimentais de machos e fêmeas. Os preás receberam 0,01 g/kg-1 de letrozol diluído, via oral, semanalmente, até as idades de 30, 45, 90 e 120 dias. O letrozol aumentou o ganho de peso corporal, das gônadas e do cérebro. Também, prejudicou a formação do epitélio germinativo testicular e estratificou o epitélio de revestimento do ovário. Ainda, o inibidor pode alterar os campos neurais relacionados às zonas de aromatização. E alterou os sítios de atuação da aromatase nas gônadas. Concluímos que o uso prolongado do letrozol pode ocasionar efeito anabólico, infertilidade de machos, induzir a displasia ovariana em fêmeas e alterar os sítios de atuação da aromatase.
Title in English
Effect of letrozole in hypothalamus and gonads of spixs yellow-toothed cavy during sexual development
Keywords in English
Anabolic effect
Aromatase
Dysplasia
Estrogens
Infertility
Abstract in English
Letrozole is used as a therapeutic in reproductive disorders caused by high estrogen levels. The enzyme cytochrome P450 aromatase biosynthesizes estrogens from androgens on tissues with steroidogenic capacity such as brain, testis and ovary. The objective of our study was to evaluate whether letrozole affects the development of the main reproductive control pathway of male and female spixs yellow-toothed cavy. For this, we considered body weight, testis, ovary and brain gain, spermatogenesis and folliculogenesis, as well as the enzymatic activity of cytochrome P450 aromatase in these tissues compared to experimental groups of males and females. The cavies received dilute letrozole orally (0,01 g/kg-1), once a week, until 30, 45, 90 and 120 days. Letrozole increased body weight, gonad and brain gain. Also, it impaired the formation of the testicular germinal epithelium and epithelium of ovary. Furthermore, the inhibitor may alter the neural fields related to the aromatization zones and changed the sites of aromatase in the gonads. We concluded that prolonged use of letrozole may result in an anabolic effect, male infertility, induce ovarian dysplasia in females, and alter the sites of aromatase activity.
 
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Publishing Date
2018-03-22
 
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