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Mol Cell Endocrinol ; 541: 111526, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34856344

RESUMO

Testicular aromatase catalyzes the synthesis of estradiol, which contributes to regulation of porcine Sertoli cell proliferation and postpubertal maintenance of Sertoli cell numbers. Although aromatase enzymatic activity decreases with age and is persistently reprogrammed by prepubertal treatment with the aromatase inhibitor letrozole, the molecular bases for regulation have not been identified. DNA methylation was examined as a potential regulatory mechanism using DNA from Leydig cells isolated from 16-, 40-, and 68-week-old boars and from 68- week-old littermates treated with the aromatase inhibitor, letrozole. Methylation levels of individual CpG dinucleotides located in the distal untranslated exon 1 of the relevant aromatase encoding gene, CYP19A3, were quite high in Leydig cell DNA, and increased further with maturity of boar (P < 0.05), while aromatase activity and transcript abundance decreased more than two-fold. However, reduced aromatase activity following letrozole treatment was not accompanied by altered DNA methylation. Testicular expression of miR378 was altered by prepubertal treatment with letrozole. The data provide evidence for two different epigenetic mechanisms that regulate aromatase expression and enzymatic activity in the boar testis.


Assuntos
Aromatase/genética , Epigênese Genética/fisiologia , Suínos/genética , Testículo/metabolismo , Animais , Animais Recém-Nascidos , Aromatase/metabolismo , Inibidores da Aromatase/farmacologia , Células Cultivadas , Epigênese Genética/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Letrozol/farmacologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Suínos/crescimento & desenvolvimento , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento
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