The Impact of Pesticides - Academy Publish

important IGFBP for binding IGF-1 in plasma, complexed with a third protein calledacid-labile subunit (ALS). Higher plasma levels of this protein have been implicated inreduced incidence of cancer by virtue of its lowering free IGF-1 levels (Morimoto etal. 2005). It is important to point out that although the majority of research has focusedon the role of IGFBPs in modulating IGF activity, IGFBPs have recently been shownto possess IGF-independent actions of their own (Bach et al. 2005).Physiologically, IGF-I serum values are low at birth, rise during childhood with peaklevels during puberty, and decline gradually with age thereafter, reaching a plateau inearly adulthood (Hoppe et al., 2004; Löfqvist et al., 2005; Rogers et al., 2005;Chellakooty et al., 2006). Puberty has been suggested as a sensitive period for theprogramming of adult IGF-1 levels. Indeed, IGF-1 peak levels at puberty seem todetermine IGF-1 levels in adulthood (Sandhu et al., 2006). An inverse relationshipbetween age and IGF-I has been described (Baibas et al., 2003; Lukanova et al., 2001;Holmes et al., 2002), the same as the existence of a sexual dimorphism with respect toIGF-I levels, with men having higher levels than women, especially in older people(Landin-Wilhemsen et al., 1994; Kaklamani et al.,1999). In this sense, estrogens seemto exert an evident effect on GH/IGF system (Scarth 2006). Estrogens induce GHsecretion, and, as a consequence, levels of GH vary with the menstrual cycle and theincreased estradiol levels are correlated with higher GH, but not IGF-1, concentrations(Lissett and Shalet, 2003). In fact, estrogens seem to exert an inhibitory effect on IGF-1 serum levels (Scarth, 2006). As a consequence, there is a negative associationbetween estrogens and IGF-I and a positive association between androgens and IGF-I(Scarth, 2006). Thus, adult women show, physiologically, lower levels of IGF-I thanadult men.As a consequence of the previously reported data, elevated GH/IGF activity couldinduce deleterious effects for human beings. A relevant side effect of elevated GH/IGFactivity also seems to be an increased incidence of various cancers such as those of theprostate, endometrium, breast, lung, prostate, cervical and colorectal cancer (Scarth,2006). Furthermore, IGF-1 has been involved in the development of other pathologiesincluding diabetes, osteoporosis, dementia and cognitive disease, and renal andcardiovascular diseases (Vaessen et al., 2001; Renehan et al., 2004; Sunyer et al.,2005; Renehan et al., 2006; Landi et al., 2007). In children alterations in the levels ofIGF-I have also been related to asthma and alterations in growth.There is a close relationship between diet, and GH/IGF system. Thus, many studiesseem to indicate that IGF-1 may mediate the association between protein intake andgrowth in children, and evidence suggest that protein restriction results in low IGF-1concentrations in healthy children (Smith et al., 1995). Therefore, dietary restrictiondecreases the serum concentration of IGF in both human and animals (Fontana et al.,2009). Whereas it is well known that serum levels of IGF-1 are clearly influenced bydietary and lifestyle factors (Kaklamani et al., 1999; Baibas et al., 2003), the effects ofxenobiotic exposure on the GH–IGF axis has not been enough explored.Currently, human beings are potentially exposed to a large range of structurallydiverse compounds. Long-term exposure to these pollutants, mainly throughenvironmental and dietetic means, potentially could modulate the GH/IGF axis. In thisAcademyPublish.org - The Impact of Pesticides144