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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Pubertal delay in male nonhuman primates (Macaca mulatta) treated with methylphenidate
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Pubertal delay in male nonhuman primates (Macaca mulatta) treated with methylphenidate

机译：哌醋甲酯治疗雄性非人类灵长类动物（猕猴）的青春期延迟

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摘要

Juvenile male rhesus monkeys treated with methylphenidate hydrochlorjde (MPH) to evaluate genetic and behavioral toxicity were observed after 14 mo of treatment to have delayed pubertal progression with impaired testicular descent and reduced testicular volume. Further evaluation of animals dosed orally twice a day with (i) 0.5 mL/kg of vehicle (n = 10), (ii) 0.15 mg/kg of MPH increased to 2.5 mg/kg (low dose, n = 10), or (iii) 1.5 mg/kg of MPH increased to 12.5 mg/kg (high dose, n = 10) for a total of 40 mo revealed that testicular volume was significantly reduced (P < 0.05) at months 15 to 19 and month 27. Testicular descent was significantly delayed (P < 0.05) in the high-dose group. Significantly lower serum testosterone levels were detected in both the low- (P= 0.0017) and high-dose (P= 0.0011) animals through month 33 of treatment. Although serum inhibin B levels were increased overall in low-dose animals (P = 0.0328), differences between groups disappeared by the end of the study. Our findings indicate that MPH administration, beginning before puberty, and which produced clinically relevant blood levels of the drug, impaired pubertal testicular development until ~5 y of age. It was not possible to resolve whether MPH delayed the initiation of the onset of puberty or reduced the early tempo of the developmental process. Regardless, deficits in testicular volume and hormone secretion disappeared over the 40-mo observation period, suggesting that the impact of MPH on puberty is not permanent.
机译：在治疗14个月后，观察到用哌醋甲酯盐酸盐（MPH）处理的幼年雄性恒河猴，以评估其青春期发育延迟，睾丸后代受损，睾丸体积减小，以评估其遗传和行为毒性。对每天两次口服（i）0.5 mL / kg媒介物（n = 10），（ii）0.15 mg / kg MPH增加到2.5 mg / kg（低剂量，n = 10）的动物进行进一步评估（iii）MPH从1.5 mg / kg增加到12.5 mg / kg（大剂量，n = 10），共40个月，表明睾丸体积在第15到19个月和第27个月显着降低（P <0.05）。大剂量组睾丸下降明显延迟（P <0.05）。到治疗的第33个月，在低剂量（P = 0.0017）和高剂量（P = 0.0011）动物中均检测到明显降低的血清睾丸激素水平。尽管低剂量动物的血清抑制素B水平总体升高（P = 0.0328），但研究结束时两组之间的差异消失了。我们的发现表明，从青春期开始就开始使用MPH，并且会产生与临床相关的药物血药水平，直到约5岁为止，青春期睾丸的发育都会受到损害。无法确定MPH是否延迟了青春期的发作或降低了发育过程的早期节奏。无论如何，在40个月的观察期内，睾丸体积和激素分泌的不足消失了，这表明MPH对青春期的影响不是永久性的。

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  • 作者

    Donald R. Mattison; Tony M. Plant; Hui-Min Lin; Hung-Chia Chen; James J. Chen; Nathan C. Twaddle; Daniel Doerge; William Slikker Jr; Ralph E. Patton; Charlotte E. Hotchkiss; Ralph J. Callicott; Steven M. Schrader; Terry W. Turner; James S. Kesner; Benedetto Vitiello; Dayton M. Petibone; Suzanne M. Morris;

  • 作者单位

    Epidemiology Branch, Division of Epidemiology, Statistics, and Prevention Research, The Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;

    Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Women's Research Institute, University of Pittsburgh, Pittsburgh, PA 15213;

    National Center for Toxicological Research, Jefferson, AR 72079;

    National Center for Toxicological Research, Jefferson, AR 72079;

    National Center for Toxicological Research, Jefferson, AR 72079;

    National Center for Toxicological Research, Jefferson, AR 72079;

    National Center for Toxicological Research, Jefferson, AR 72079;

    National Center for Toxicological Research, Jefferson, AR 72079;

    Toxicologic Pathology Associates, Jefferson, AR 72079;

    Bionetics Corporation, Jefferson, AR 72079;

    Bionetics Corporation, Jefferson, AR 72079;

    Division of Applied Research and Technology, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, OH 45226;

    Division of Applied Research and Technology, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, OH 45226;

    Division of Applied Research and Technology, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, OH 45226;

    National Institute of Mental Health, Bethesda, MD 20892-9633;

    National Center for Toxicological Research, Jefferson, AR 72079;

    National Center for Toxicological Research, Jefferson, AR 72079;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    attention deficit hyperactivity disorder; developmental delay; male puberty;

    机译：注意缺陷多动障碍;发展迟缓;男性青春期;

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