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Título: | Effect of treatment with the selective oestrogen receptor modulator LY117018-HCl on pituitary sensitivity to GnRH and subsequent ovulation |
Autor: | Hernández, G.; Hernández-Jiménez, J. G.; Martínez-Morales, Juan Ramón CSIC ORCID; Alonso, Rafael | Palabras clave: | Diestrus Estradiol Gonadotropin-releasing hormone Luteinizing hormone Ovariectomy Ovulation Pituitary gland Pyrrolidines Selective estrogen receptor modulators LY 117018 |
Fecha de publicación: | 1-abr-2003 | Editor: | Society for Reproduction and Fertility | Citación: | Reproduction 125(4): 597-606 (2003) | Resumen: | The effects of LY117018-HCl (LY; a benzothiophene similar to raloxifene) were examined on various reproductive parameters in female rats. Four-day cyclic rats were treated (10:00 h on dioestrus) with LY (0.01, 0.1, 0.5, 1, 2, 4 or 16 mg kg(-1) p.o.) and assessed for ovulation at oestrus. LY inhibited ovulation at doses as low as 0.5 mg kg(-1), and ovulation did not occur at doses of 4 and 16 mg kg(-1). LY (16 mg kg(-1)) reduced wet uterine mass and LH concentrations at the time of the expected ovulatory surge. Ovulation induced by hCG in pentobarbital-treated rats was not altered by LY treatment, indicating normal ovarian sensitivity to gonadotrophins. LY, however, completely blocked the effects of oestradiol (under either negative or positive feedback modes) on LH secretion in ovariectomized rats. GnRH secretion into hypophyseal portal blood during pro-oestrus was not affected by treatment with LY, whereas the concentrations of serum LH remained reduced. Finally, treatment with LY markedly reduced pituitary sensitivity to GnRH during pro-oestrus, as it completely blocked GnRH-induced LH secretion. These results demonstrate that LY inhibits oestradiol action in the uterus and prevents ovulation in normal cyclic rats. LY-induced inhibition of ovulation is not caused by an alteration of the ovarian response to gonadotrophins or an impairment of GnRH secretion at the hypothalamus, but by a reduction in the sensitivity of gonadotrophs to the stimulatory effects of GnRH during pro-oestrus. | Descripción: | 10 páginas, 5 figuras, 2 tablas.-- et al. | Versión del editor: | http://dx.doi.org/10.1530/rep.0.1250597 | URI: | http://hdl.handle.net/10261/41532 | DOI: | 10.1530/rep.0.1250597 | ISSN: | 1470-1626 | E-ISSN: | 1741-7899 |
Aparece en las colecciones: | (CABD) Artículos |
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