REGULATION OF HUMAN DERMAL PAPILLA CELL PRODUCTION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 BY RETINOIC ACID, GLUCOCORTICOIDS, AND INSULIN-LIKE GROWTH-FACTOR-I

Insulin-like growth factor-1 (IGF1) has been reported to stimulate hai r elongation and to facilitate maintenance of the hair follicle in ana gen phase. However, little is known about IGF1 signaling in the hair f ollicle. In this study we investigate the effects of IGF1, glucocortic oids, and retinoids on dermal papilla (DP) cell production of insulin- like growth factor binding proteins (IGFBPs). IGFBPs comprise a family of IGF binding proteins that are produced and released by most cell t ypes. They bind to IGFs to either enhance or inhibit IGF activity. In the present report we identify IGFBP-3 as being produced and released by cultured human dermal papilla (DP) cells. IGFBP-3 levels are increa sed fivefold by retinoic acid, eightfold by dexamethasone, and tenfold by IGF1. DP cells are known to produce IGF1, and so the observed stim ulation of DP cell IGFBP-3 production by IGF1 is consistent with the i dea that DP cells possess the IGF transmembrane receptor kinase and ar e autoregulated by IGFs. The level of another IGFBP, tentatively ident ified as IGFBP-2, is, in contrast, not regulated by these agents. IGFB P-3 has been shown to inhibit the activity of IGFs in a variety of sys tems. Our results are consistent with a model in which retinoids and g lucocorticoids inhibit IGF action on DP cells and surrounding matrix c ells by stimulating increased DP cell production of IGFBP-3. The IGFBP -3, in turn, forms a complex with free IGF1 to reduce the concentratio n of IGF1 available to stimulate hair elongation and maintenance of an agen phase. (C) 1996 Wiley-Liss, Inc.