Response to Ben Amitai et al.

Abstract

Whereas IGF-I has been initially described as a potent mitogen supporting cell growth and survival (Stewart and Rotwein, 1996), there is accumulating evidence for its participation in diverse differentiation processes (Musaro and Rosenthal, 1999; Hsieh et al., 2004). Our recent work on IGF-I confirmed this dual role for the murine hair follicle (Weger and Schlake, 2005a, 2005b). In man, an IGF-I deficiency is associated with Laron syndrome (Laron, 2002). Interestingly, patients show impaired hair production and structural abnormalities of hair shafts (Lurie et al., 2004). On the molecular level, people with Laron syndrome are similar to Ivl::Igfbp3 mice that are supposed to have reduced levels of freely available IGF-I. The suppression of endogenous signalling in these mice causes a remarkable thinning of hair shafts that has been also described for Laron syndrome (Lurie et al., 2004; Weger and Schlake, 2005b); by contrast, overexpression of Igf-I appeared to increase murine hair thickness (Weger and Schlake, 2005a). However, other structural defects of hair shafts were only observed in Ivl::Igf-I mice (Weger and Schlake, 2005a); Ivl::Igfbp3 hair shafts looked fairly normal as opposed to hair from Laron syndrome patients (Lurie et al., 2004; Weger and Schlake, 2005b). This discrepancy between man and mouse might be owing to several reasons: firstly, it may point to a fundamental difference between these species. Actually, there is already precedence for structural diversity; whereas the murine hair shaft medulla forms easily visible air spaces during differentiation, they are lacking in human hair. Secondly, it is possible that the obtained suppression of IGF-I signalling in Ivl::Igfbp3 mice is lower than in people suffering from Laron syndrome. However, data on mouse lines with significantly different expression levels of Igfbp3 suggest that effects are restricted to quantitative alterations of hair length and thickness. Thirdly, the primary defect giving rise to Laron syndrome is a block of growth hormone signalling (Laron, 2002). Thus, some abnormalities might be not owing to IGF-I deficiency. As growth factors share many intracellular signalling pathways, a partial compensation of such defects by IGF-I treatment might be possible. Consequently, interpretation of data on Laron syndrome has to be very cautious with respect to IGF-I's role in human hair follicles. Although similarities regarding IGF-I and hair production are apparent between man and mouse, a detailed comparative analysis is still missing.