ABSTRACT Studies assessing the consequences of manganese (Mn) deficiency have generally revealed that this element is important for mammalian reproduction, but little attention has been devoted to assessing its potential effects during pubertal development. Because Mn is capable of crossing the blood brain barrier and accumulating in the hypothalamus, and since infants and children are suspected of being more sensitive to this element, we recently questioned whether Mn could influence the hypothalamus just prior to the onset of puberty. This review describes a series of both acute and chronic Mn exposure studies showing that this element can indeed act within the hypothalamus to control important prepubertal events. Specifically, both in vitro and in vivo methods have revealed that MnCl2 can acutely stimulate the secretion of luteinizing hormone releasing hormone (LHRH) and luteinizing hormone (LH), respectively, in prepubertal female rats. The chronic effect of low-dose Mn supplementation has also been shown to stimulate specific serum hormones and cause precocious pubertal development. Finally, in vitro studies have demonstrated that the hypothalamic mechanism of action to induce prepubertal LHRH secretion is through activation of soluble guanylyl cyclase, resulting in the stimulation of the cGMP-protein kinase G (PKG) pathway. These effects of Mn in immature females are also discussed in relation to dose and gender differences observed in subsequent studies using immature and adult male rats, and furthermore, considerations concerning the potential for Mn and precocious pubertal development will be discussed.
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