IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
 Inhibition of Cytochrome P450C17 (CYP 17) enzyme by a Gonadotropin-releasing hormone (GnRH-I) agonist in ovarian follicles from gonadotropin-stimulated rats
Autor/es:
IRUSTA G; PARBORELL F; TESONE M
Revista:
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Referencias:
Año: 2007 vol. 292 p. 1456 - 1464
ISSN:
0193-1849
Resumen:
Our objective was to study the direct action of a GnRH-I agonist, Leuprolide Acetate (LA), on ovarian steroidogenesis in preovulatory follicles obtained from equine Chorionic Gonadotropin (eCG)-treated rats. Previously, we have demonstrated an inhibitory effect of LA on steroidogenesis and follicular development. In this study, we tested the hypothesis that GnRH exerts its negative effect on follicular development by inhibiting thecal P450C17 á-hydroxylase expression and, consequently, androgen synthesis. Studies were carried out in prepubertal female rats injected with either eCG (control) or eCG+LA (LA) and sacrificed at different time points. Immunohistochemical studies indicated that LA induced StAR (steroidogenic acute regulatory protein) expression, mainly in theca cells of preantral and antral follicles. In addition, serum progesterone levels increased significantly (p<0.05), while those of androsterone decreased (p<0.05) after 8h of LA treatment. This inhibition caused by LA seemed to be a consequence of the decreased expression of follicular P450C17 á-hydroxylase as demonstrated by western blot and RT-PCR techniques. In vitro studies using follicles isolated from 48h-eCG-treated rats and cultured with LA, showed a significant (p<0.05) inhibition of FSH–induced androsterone follicular content, as well as P450C17 á-hydroxylase protein levels as determined by western analysis. However, LA increased StAR protein expression in these follicles without significant changes in P450scc enzyme levels. Taking all these findings into account, we suggest that GnRH-I exerts a direct inhibitory action on gonadotropin-induced follicular development by decreasing the temporal expression of the P450C17 enzyme and, consequently, androgen production, thus reducing the supply of estrogens available to developing follicles.