Differential effects of manganese and alcohol on mammalian pubertal development

Abstract

The age at which the onset of puberty begins is variable and depends on a complex series of centrally mediated events resulting in an increased pulsatile pattern of luteinizing hormone releasing hormone (LHRH) secretion from the hypothalamus. This changing pattern in LHRH secretion at puberty has been associated with the removal of an inhibitory tone and/or with the developmental responsiveness to excitatory components within the hypothalamus. In recent years much progress has been made in identifying inhibitory components such as gamma aminobutyric acid and the opioid peptides (1, 2), as well as stimulatory components such as excitatory amino acids (3), leptin (4), transforming growth factor a (TGFa; 5), insulin like growth factor -1 (IGF-1; 6), KiSS-1/kisspeptin (7) and manganese (Mn; 8). Importantly, all of these substances are capable of influencing LHRH secretion at puberty. The increased release of LHRH at puberty appears to utilize an interactive participation of neural circuits and glial cells (9). Furthermore, it is well known that neuronal and glial functions can be further influenced by peripheral metabolic signals, genetic and environmental influences, as well as drugs of abuse. Thus, any substance, whether it be endogenous or exogenous, that is capable of stimulating or inhibiting prepubertal LHRH secretion could have an impact on pubertal development. In recent years we have studied the actions of manganese chloride (MnCl₂), IGF-1 and alcohol (ALC) on puberty related events. This article will review our current understanding of the positive and/or negative influences of each of these substances on pubertal processes in females. Specifically, we will describe the positive action of MnCl₂ on LHRH release, and point out the potential beneficial and harmful effects of prepubertal exposure to low but elevated levels of this element. We will also describe the positive role of IGF-1 on puberty, and the negative action of prepubertal ALC exposure during pubertal development. Furthermore, we will discuss the actions and interactions between ALC and IGF-1 on puberty related genes, hormonal secretions and the timing of female puberty.