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Abstract:

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 gonadotropin-releasing hormone (GnRH) exerts its negative effect on follicular development by inhibiting thecal cytochrome P-450 C17 (P450C17) α-hydroxylase expression and, consequently, androgen synthesis. Studies were carried out in prepubertal female rats injected with either eCG (control) or eCG plus LA (LA) and killed at different time points. Immunohistochemical studies indicated that LA induced steroidogenic acute regulatory protein (StAR) expression mainly in theca cells of preantral and antral follicles. In addition, serum progesterone levels increased significantly (P < 0.05), whereas those of androsterone decreased (P < 0.05) after 8 h of LA treatment. This inhibition caused by LA seemed to be a consequence of the decreased expression of follicular P450C17 α-hydroxylase, as demonstrated by Western blot and RT-PCR techniques. In vitro studies using follicles isolated from 48-h-eCG-treated rats and cultured with LA showed a significant (P < 0.05) inhibition of FSH-induced androsterone follicular content as well as P450C17 α-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. Copyright © 2007 the American Physiological Society.

Registro:

Documento: Artículo
Título:Inhibition of cytochrome P-450 C17 enzyme by a GnRH agonist in ovarian follicles from gonadotropin-stimulated rats
Autor:Irusta, G.; Parborell, F.; Tesone, M.
Filiación:Instituto de Biología Y Medicina Experimental, Consejo Nacional de Investigaciones Científicas Y Técnicas, Universidad de Buenos Aires, Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas, Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto de Biología Y Medicina Experimental, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:Follicle; Gonadotropin-releasing hormone agonist; Ovary; Steroidogenesis; androgen; androsterone; cytochrome P450; gonadorelin; gonadorelin agonist; gonadotropin; leuprorelin; steroidogenic acute regulatory protein; animal experiment; article; controlled study; enzyme inhibition; female; gene expression; immunohistochemistry; nonhuman; ovary follicle; priority journal; progesterone blood level; rat; reverse transcription polymerase chain reaction; steroidogenesis; Western blotting; Androsterone; Animals; Blotting, Western; Female; Gonadotropin-Releasing Hormone; Gonadotropins, Equine; Horses; Immunohistochemistry; Leuprolide; Ovarian Follicle; Phosphoproteins; Progesterone; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA; Steroid 17-alpha-Hydroxylase
Año:2007
Volumen:292
Número:5
Página de inicio:E1456
Página de fin:E1464
DOI: http://dx.doi.org/10.1152/ajpendo.00226.2006
Título revista:American Journal of Physiology - Endocrinology and Metabolism
Título revista abreviado:Am. J. Physiol. Endocrinol. Metab.
ISSN:01931849
CODEN:AJPMD
CAS:androsterone, 53-41-8; cytochrome P450, 9035-51-2; gonadorelin, 33515-09-2, 9034-40-6; gonadotropin, 63231-54-9; leuprorelin, 53714-56-0, 74381-53-6; steroidogenic acute regulatory protein, 168183-61-7; Androsterone, 53-41-8; Gonadotropin-Releasing Hormone, 33515-09-2; Gonadotropins, Equine; Leuprolide, 53714-56-0; Phosphoproteins; Progesterone, 57-83-0; RNA, 63231-63-0; Steroid 17-alpha-Hydroxylase, EC 1.14.99.9; steroidogenic acute regulatory protein
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01931849_v292_n5_pE1456_Irusta

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Citas:

---------- APA ----------
Irusta, G., Parborell, F. & Tesone, M. (2007) . Inhibition of cytochrome P-450 C17 enzyme by a GnRH agonist in ovarian follicles from gonadotropin-stimulated rats. American Journal of Physiology - Endocrinology and Metabolism, 292(5), E1456-E1464.
http://dx.doi.org/10.1152/ajpendo.00226.2006
---------- CHICAGO ----------
Irusta, G., Parborell, F., Tesone, M. "Inhibition of cytochrome P-450 C17 enzyme by a GnRH agonist in ovarian follicles from gonadotropin-stimulated rats" . American Journal of Physiology - Endocrinology and Metabolism 292, no. 5 (2007) : E1456-E1464.
http://dx.doi.org/10.1152/ajpendo.00226.2006
---------- MLA ----------
Irusta, G., Parborell, F., Tesone, M. "Inhibition of cytochrome P-450 C17 enzyme by a GnRH agonist in ovarian follicles from gonadotropin-stimulated rats" . American Journal of Physiology - Endocrinology and Metabolism, vol. 292, no. 5, 2007, pp. E1456-E1464.
http://dx.doi.org/10.1152/ajpendo.00226.2006
---------- VANCOUVER ----------
Irusta, G., Parborell, F., Tesone, M. Inhibition of cytochrome P-450 C17 enzyme by a GnRH agonist in ovarian follicles from gonadotropin-stimulated rats. Am. J. Physiol. Endocrinol. Metab. 2007;292(5):E1456-E1464.
http://dx.doi.org/10.1152/ajpendo.00226.2006