Abstract
The purpose of this investigation was to determine the estrogenic and antiestrogenic activities of the potential contraceptive agent anordiol in the immature rat. A dose of 2.45 μmol of anordiol (AD), estradiol (E2), clomiphene citrate (CC), tamoxifen (TA), or the vehicle alone was administered to rats on the 25th and 29th days of age. Serum hormones were measured between 16∶00 and 17∶00 on days 30, 31, and 32; organ weights were determined on day 32. Anordiol and estradiol treatments significantly increased ovarian and uterine weight and serum LH concentrations, but CC and TA had no effect on these parameters. Vaginal cornification occurred before day 32 in all rats receiving anordiol or estradiol and in 3/5 and 4/5 rats receiving CC and TA, respectively, but not in control rats. Based on serum progesterone levels, ovulation was induced only in rats receiving anordiol or estradiol. All of the compounds tested significantly increased serum testosterone above levels in control animals, but both AD and E2 induced ovulation without a further increase in serum testosterone. We conclude that in the immature rat anordiol produces estrogenic responses in the vagina, uterus and in the hypothalamic-pituitary-ovarian axis, whereas TA and CC are estrogenic only on the vaginal and uterine epithelium.
Resumé
L'objectif de cette étude était de déterminer l'activité oestrogène et anti-oestrogène de l'eventuel agent contraceptif anordiol chez des rats immatures. On a administré à des rats femelles âgés de 25 et 29 jours, une dose de 2,45 μmoles d'anordiol, oestradiol, citrate de climiphène (CC), tamoxifène (TA), ou du seul excipient. Les hormones sériques ont été mesurées entre 16 heures et 17 heures aux jours 30, 31 et 32; le poids des organes a été contrôlé au trente-deuxième jour. Les traitments à l'anordiol et à l'oestradiol ont provoqué une augmentation pondérale significative des ovaires et de l'utérus et une élévation des concentrations sériques de LH; le CC et le TA n'ont cependant eu aucun effect sur ces paramètres. La racornissement vaginal s'est produit avant le trent-deuxième jour chez tous les animaux ayant reçu l'anordiol ou l'oestradiol, et respectivement chez 3/5 et chez 4/5 de ceux ayant reçu du CC ou du TA, mais non chez les témoins. D'après les niveaux de la progestérone sérique, l'ovulation n'a été induite que chez les rats traités à l'anordiol ou l'oestradiol. Tous les composants testés ont provoqué une élévation significative de la testostérone sérique à dess niveaux supérieurs à ceux retrouvés dans les animaux témoins, mais l'AD et l'E2 ont l'un et l'autre provoqué l'ovulation sans augmentation supplémentaire de la testostérone sérique. Nous en concluons que, chez les rats immatures, l'anordiol entraîne une réaction oestrogène dans la vagin, dans l'utérus et dans l'axe hypothalamus-pituitaire-ovarien, alors que la réaction au TA et au CC n'est oestrogène que sur l'épithélium du vagin et de l'utérus.
Resumen
El objetivo de esta investigación era determinar la actividad estrógena y antiestrógena del agente anticonceptive potencial anordiol en la rata inmadura. Se administró a ratas una dosis de 2,45 μmoles de anordiol, estradiol, clomifen citrato (CC), tamoxifen (TA) o el vehículo solamente a los 25 y 29 días de edad. Las hormonas séricas se midieron entre las 16.00 y las 17.00 hs en los días 30, 31 y 32; el peso de los órganos se determinó en el día 32. Los tratamientos con anordiol y estradiol aumentaron significativamente el peso de los ovarios y del útero y las concentraciones séricas de LH pero el CC y el TA carecieron de efecto sobre estos parámetros. La cornificación vaginal ocurrió antes del día 32 en todas las ratas a las que se había administrado anordiol o estradiol y en 3/5 y 4/5 de las ratas a las que se había administrado CC y TA, respectivamente, pero no en las ratas control. En base a los niveles de progesterona sérica, la ovulacióm se indujo sólo en las ratas a las que se administraba anordiol o estradiol. Todos los compuestos sometidos a prueba aumentaron significativamente la testosterona sérica por encima de los niveles de los controles pero tanto el AD como el E2 indujeron la ovulación sin un incremento adicional de la testosterona sérica. Llegamos a la conclusión de que en la rata, inmadura el anordiol produce respuestas estrógenas en la vagina, el útero y el eje hipotalámico-hipofisario-ovárico, mientras que el TA y el CC son estrógenos sólo en el epitelio vaginal y uterino.
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Lu, Y.C., Chatterton, R.T. Effect of anordiol on ovarian hormone secretion, ovulation, and uterine and vaginal responses in the immature rat. Adv Contracept 10, 157–166 (1994). https://doi.org/10.1007/BF01978109
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DOI: https://doi.org/10.1007/BF01978109