Chapter 17: The Effects of Manganese on Female Pubertal Development

Manganese (Mn) is a naturally occurring essential trace element required for normal physiological processes. Both excesses and deficiencies of Mn are known to affect brain functions and are associated with health-related problems. For years it has been recognized that laboratory animals which are deficient in Mn show signs of impaired growth and reproduction. Because this element can cross the blood–brain barrier more efficiently in the young than in adult animals, and since it can accumulate in the hypothalamus, we have assessed the effects of low level Mn exposure on the onset of pubertal development. The age at which normal puberty occurs depends on a complex series of events within the hypothalamus that culminate in the increased synthesis and release of gonadotropin-releasing hormone (GnRH). This chapter will describe the action of prepubertal Mn exposure in inducing precocious puberty. Additionally, we will discuss the physiological and molecular mechanisms by which Mn can activate specific upstream puberty-related genes regulating hypothalamic GnRH synthesis and release. Our results are discussed in terms of how low level Mn exposure, resulting in a modest accumulation of the element within the hypothalamus too early in life, may cause a potential risk for developing precocious puberty.