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婴儿期暴露于4-叔辛基苯酚会短暂抑制大鼠卵巢类固醇生成及类固醇生成急性调节蛋白(StAR)的表达。

Infantile 4-tert-octylphenol exposure transiently inhibits rat ovarian steroidogenesis and steroidogenic acute regulatory protein (StAR) expression.

作者信息

Myllymäki S A, Karjalainen M, Haavisto T E, Toppari J, Paranko J

机构信息

Department of Biology, Laboratory of Animal Physiology, 20014 University of Turku, Finland.

出版信息

Toxicol Appl Pharmacol. 2005 Aug 22;207(1):59-68. doi: 10.1016/j.taap.2004.12.001.

Abstract

Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg) subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening.

摘要

酚类化合物,如4-叔辛基苯酚(OP),已被证明会干扰大鼠卵巢类固醇生成。然而,关于婴儿期接触OP对未成熟卵巢类固醇生成的影响知之甚少。本研究的目的是调查婴儿期接触OP对14日龄雌性大鼠血浆促卵泡激素(FSH)、促黄体生成素(LH)、雌二醇和孕酮水平的影响。通过蛋白质免疫印迹法分析对卵巢类固醇生成急性调节蛋白(StAR)和FSH受体(FSHr)表达的影响。对卵泡雌二醇、孕酮、睾酮和环磷酸腺苷(cAMP)生成进行体外分析。在出生后第6、8、10和12天,给斯普拉格-道利大鼠皮下注射OP(0、10、50或100mg/kg)。在出生后第14天,当OP剂量为100mg/kg时,血浆FSH降低,孕酮显著升高。此外,最高OP剂量使青春期阴道开口时间提前。OP对婴儿期LH和雌二醇水平或卵巢FSHr含量没有影响。与对照组相比,所有OP剂量下卵巢StAR蛋白含量以及体外激素和cAMP生成均降低。然而,在长时间培养过程中,激素水平独立于FSH恢复,甚至升高至高于对照水平。在出生后第35天,对照组和接触OP的动物在血浆FSH、LH、雌二醇和孕酮水平或卵巢StAR蛋白含量方面没有统计学上的显著差异。结果表明,OP对婴儿期卵巢的影响是可逆的,而如前所述,在下丘脑和垂体中更持久的影响参与了循环FSH水平的降低和阴道过早开口。

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