info:eu-repo/semantics/article
Treatment with the synthetic PPARG ligand pioglitazone ameliorates early ovarian alterations induced by dehydroepiandrosterone in prepubertal rats
Fecha
2019-02Registro en:
Velez, Leandro Martin; Abruzzese, Giselle Adriana; Heber, María Florencia; Ferreira, Silvana Rocio; Motta, Alicia Beatriz; Treatment with the synthetic PPARG ligand pioglitazone ameliorates early ovarian alterations induced by dehydroepiandrosterone in prepubertal rats; Polish Acad Sciences Inst Pharmacology; Pharmacological Reports; 71; 1; 2-2019; 96-104
1734-1140
CONICET Digital
CONICET
Autor
Velez, Leandro Martin
Abruzzese, Giselle Adriana
Heber, María Florencia
Ferreira, Silvana Rocio
Motta, Alicia Beatriz
Resumen
Background: Peroxisome proliferator-activated receptor gamma (PPARG) is a nuclear factor that may act on the early development of ovarian follicles and on follicular steroidogenesis. However, the exact mechanism of PPARG action remains unknown. We have previously found that androgen excess alters early ovarian function and the PPARG system. The aim of the present study was to evaluate whether PPARG activation (using the synthetic ligand pioglitazone (PGZ)) ameliorates the alterations in early ovarian function induced by androgen excess. Methods: Female prepubertal rats were treated with equine chorionic gonadotropin (eCG) to induce folliculogenesis, together with dehydroepiandrosterone (DHEA) to induce hyperandrogenism and/or PGZ to evaluate PPARG activation. We assessed i) very early ovarian folliculogenesis, ii) PPARG activation, iii) ovarian steroidogenic enzymes, iv) the estradiol/testosterone ratio, v) the ovarian inflammatory status and vi) oxidative stress. Results: PGZ prevented the inactivation of ovarian PPARG induced by androgen excess by increasing PPARG itself and the gene expression of PPARG-coactivator 1 alpha (PGC1A), and by decreasing the gene expression of nuclear co-repressor (NCOR). PGZ also prevented the altered ovarian steroidogenesis, pro-inflammatory status and oxidative stress induced by androgen excess. Conclusions: Our findings suggest that PPARG activation plays important roles in modulating early ovarian function, and highlight the importance of understanding the role(s) of PPARG activation in the ovary, and the possible involvement in the treatment of ovarian pathologies, and/or the impact in regulating/improving fertility.