Pine Michelle, Lee Boyeon, Dearth Robert, Hiney Jill K, Dees W Les
Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas 77843-4458, USA.
Toxicol Sci. 2005 Jun;85(2):880-5. doi: 10.1093/toxsci/kfi134. Epub 2005 Mar 2.
Manganese (Mn), an essential element considered important for normal growth and reproduction, has been shown in adults to be detrimental to reproductive function when elevated. Because Mn can cross the blood-brain barrier and accumulate in the hypothalamus, and because it has been suggested that infants and children are potentially more sensitive to Mn than adults, we wanted to determine the effects of Mn exposure on puberty-related hormones and the onset of female puberty. We demonstrated that MnCl(2) when administered acutely into the third ventricle of the brain acts dose-dependently to stimulate luteinizing hormone (LH) release in prepubertal female rats. Incubation of hypothalami in vitro showed that this effect was due to a Mn-induced stimulation of luteinizing hormone releasing hormone (LHRH). Further demonstration that this is a hypothalamic site of action was shown by in vivo blockade of LHRH receptors and lack of a direct pituitary action of Mn to stimulate LH in vitro. To assess potential short-term effects, animals were supplemented with MnCl(2) (10 mg/kg) by gastric gavage from day 12 until day 29, or, in other animals, until vaginal opening (VO). Mn caused elevated serum levels of LH, follicle stimulating hormone, and estradiol, and it initiated a moderate but significant advancement in age at VO. Our results are the first to show that Mn can stimulate specific puberty-related hormones and suggest that it may facilitate the normal onset of puberty. They also suggest that Mn may contribute to precocious puberty if an individual is exposed to elevated levels of Mn too early in development.
锰（Mn）是一种对正常生长和繁殖很重要的必需元素，在成年人中已表明，锰水平升高时对生殖功能有害。由于锰可以穿过血脑屏障并积聚在下丘脑，并且有人提出婴幼儿和儿童可能比成年人对锰更敏感，因此我们想确定锰暴露对青春期相关激素和女性青春期启动的影响。我们证明，将氯化锰急性注入青春期前雌性大鼠的第三脑室时，其作用具有剂量依赖性，可刺激促黄体生成素（LH）释放。下丘脑的体外孵育表明，这种作用是由于锰诱导的促黄体生成素释放激素（LHRH）的刺激。通过体内阻断LHRH受体以及锰在体外缺乏直接刺激垂体释放LH的作用，进一步证明了这是一个下丘脑作用位点。为了评估潜在的短期影响，从第12天到第29天，通过胃管给动物补充氯化锰（10 mg/kg），或者在其他动物中，直到阴道开口（VO）。锰导致血清中LH、促卵泡激素和雌二醇水平升高，并使VO年龄适度但显著提前。我们的结果首次表明，锰可以刺激特定的青春期相关激素，并表明它可能促进青春期的正常启动。它们还表明，如果个体在发育早期接触到升高水平的锰，锰可能导致性早熟。
