094 Patterns of Insulin-like growth factor expression during murine hair follicle development and cycling

Y-C. Liu, J.J.Bull, S. Muller-Rover, M.P.Philpott. Centre for Cutaneous Research, St Bartholomew’s and the Royal London School of Medicine and Dentistry. QMW College. University of London. UK.

The insulin-like growth factors (IGF-I and IGF-II) are polypeptide growth factors that exhibit close homologies to insulin and possess potent anabolic and mitogenic effects both in vivo and in vitro. The biological effects of both IGF-I and IGF-II are mediated via the IGF-I receptor (IGF-IR), which can also be activated in vitro by supra-physiological levels of insulin. We have previously reported that cultured human hair follicles maintained in the absence of IGF-I show premature entry into catagen. Immunohistochemistry of human skin has shown that IGF-IR is expressed in the dermal papilla (DP) and matrix but not in the highly proliferative germinative epithelium. Moreover, IGF-IR expression appears to be regulated in a hair cycle dependant manner (Rudman et al 1997 JID). These data suggest that IGF-I may play an important role in regulation of the hair growth cycle. To investigate this in more detail we have studied by immunohistochemistry the patterns of expression of IGF-I, IGF-IR, IGF-II, IGF-II receptor (Mannose-6-phosphate receptor), Insulin receptor (IR) in murine hair follicles and during the murine hair growth cycle. Our key findings were that IGF-I immunoreactivity (IR) was weakly expressed in 0-5 day old skin and that a similar pattern of IGF-IR expression was also observed. In contrast IR was expressed in both In 12 day old mice (anagen). IGF-IR and IGF-I IR were detected in both the interfollicular epidermis and dermis as well as in the hair follicle epithelium (germinative epithelium, matrix and ORS) and the dermal papilla (DP) and connective tissue sheath (CTS). IR expression mirrored that of IGF-IR. Strong IGF-IIR IR was detected on the sebaceous gland. In 18 day old mice (catagen) marked downregulation of IGF-IR was detected in the receding epithelial strand, whilst the DP and permanent portion of the ORS were positive. In 24 day old mice (telogen) little IGF-I R or IGF-I IR were detected on the hair follicle epithelium. However, the DP remained positive for both IGF-I and IGF-IR. The marked downregulation seen for IGF-I and IGF-I R was also observed for the IR. This data supports our previous data and demonstrates marked changes in the patterns of IGF-I expression during the murine cycle. However, our data suggests that differences in the patterns of expression exist between murine and human hair follicles and that this may reflect differences in hair cycle control, cytokine function or possible cytokine redundancy between murine and human follicles.