Effects of p-Nonylphenol and 4-tert-Octylphenol on the Anterior Pituitary Functions in Adult Ovariectomized Rats
Effects of p-Nonylphenol and 4-tert-Octylphenol on the Anterior Pituitary Functions in Adult Ovariectomized Rats
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DOI：
10.1159/000096093
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发表时间：
2006-12
影响因子：
4.1
通讯作者：
Miyako Furuta;T. Funabashi;M. Kawaguchi;Takahiro J. Nakamura;D. Mitsushima;F. Kimura
中科院分区：
文献类型：
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作者：
Miyako Furuta;T. Funabashi;M. Kawaguchi;Takahiro J. Nakamura;D. Mitsushima;F. Kimura
对壬基苯酚 (NP) 和 4-叔辛基苯酚 (OP) 已知可模仿雌激素作为内分泌干扰物的作用。然而，它们对体内垂体和下丘脑功能的急性影响尚不确定。因此，我们确定了它们对垂体前叶的影响，特别是促性腺激素分泌的影响。卵巢切除后两周，大鼠皮下注射 10 mg NP、10 mg OP、10 mg 双酚 A、1 µg 17β-雌二醇或单独芝麻油作为对照。治疗24小时后，测定垂体前叶孕酮受体mRNA的表达以及黄体生成素（LH）、卵泡刺激素和催乳素的水平。 NP、OP、双酚A或雌二醇均可显着增加垂体前叶孕酮受体mRNA的表达，但双酚A的效果较差。 NP 或 OP 可显着降低 LH 水平，但双酚 A 和雌二醇则不会显着降低 LH 水平。只有雌二醇显着增加催乳素水平。任何治疗均未改变促卵泡激素的水平。为了检查 NP 和 OP 对脉动 LH 分泌的影响，在 3 小时内每隔 6 分钟进行一次血液采样。对切除卵巢的成年大鼠进行治疗 24 小时后，我们发现注射 NP 显着降低了 LH 脉冲的幅度和平均 LH 浓度，但没有降低 LH 脉冲的频率。 OP 的注射显着降低了平均 LH 浓度，而不影响 LH 脉冲的频率和幅度。最后，给注射NP或芝麻油的大鼠静脉注射50 ng促性腺激素释放激素（GnRH），以检查NP是否影响垂体前叶对GnRH的LH分泌反应。我们发现，与注射芝麻油的大鼠相比，注射 NP 的大鼠对 GnRH 的反应性显着减弱。目前的研究表明，即使单次注射，NP 也可能通过影响垂体前叶水平来抑制成年卵巢切除大鼠的脉动 LH 分泌。
p-Nonylphenol (NP) and 4-tert-octylphenol (OP) are known to mimic the action of estrogens as endocrine disruptors. However, their acute effects on the pituitary and the hypothalamus functions in vivo have been uncertain. We therefore determined their effects on the anterior pituitary, in particular, gonadotropin secretion. Two weeks after ovariectomy, the rats were given a subcutaneous injection of 10 mg NP, 10 mg OP, 10 mg bisphenol A, 1 µg 17β-estradiol, or sesame oil alone as control. Twenty-four hours after the treatment, the expression of progesterone receptor mRNA in the anterior pituitary and the level of luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were determined. The expression of progesterone receptor mRNA in the anterior pituitary was significantly increased by either NP, OP, bisphenol A, or estradiol, but bisphenol A was less effective. The level of LH was significantly decreased by either NP or OP, but not by bisphenol A and estradiol. Only estradiol significantly increased the level of prolactin. The level of follicle-stimulating hormone was unchanged by any of the treatments. To check the effects of NP and OP on pulsatile LH secretion, blood samplings were done at 6-min intervals for 3 h. Twenty-four hours after treatment in ovariectomized adult rats, we found that the injection of NP significantly decreased the amplitude of LH pulses and the mean LH concentrations, but not the frequency of LH pulses. The injection of OP significantly decreased the mean LH concentrations without affecting the frequency and amplitude of the LH pulses. Finally, the rats given an injection of NP or sesame oil were intravenously injected with 50 ng of gonadotropin-releasing hormone (GnRH) to check whether NP affected the LH secretory responsiveness of the anterior pituitary to GnRH. We found that the responsiveness to GnRH in NP-injected rats was significantly attenuated compared to the sesame oil-injected rats. The present study suggests that NP, even with a single injection, suppresses the pulsatile LH secretion in adult ovariectomized rats, probably by affecting the anterior pituitary level.