LOCALIZATION OF MESSENGER-RIBONUCLEIC-ACID FOR INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS IN HUMAN SKIN BY IN-SITU HYBRIDIZATION

The role of the insulin-like growth factors (IGFs) in human skin physiology has been increasingly recognized, although relatively little is known about the cell types involved or the cellular mechanisms that mediate these responses. Epidermal keratinocytes and dermal fibroblasts both possess IGF-I receptors and are responsive to IGF-I. IGF-binding proteins (IGFBPs), known modulators of IGF action, may also be responsible for targeting IGF-I to its receptors and are produced by both cultured keratinocytes and fibroblasts. To demonstrate sites of production of IGFBPs in human skin, we have used in situ hybridization to localize messenger ribonucleic acid (mRNA) for the six IGFBPs. Antisense and sense RNA probes for the IGFBPs (IGFBP-1 to -6) were produced, and 5-mu m sections of normal adult human male chest skin were probed The control probe used was keratin-5, which is known to hybridize to the basal keratinocytes of the epidermis. mRNAs for human IGFBP-2, -3, -4, and -5 were identified, with mRNAs for IGFBP-2 and IGFBP-4 localized in sebaceous glands and eccrine sweat glands (epidermal origin), IGFBP-3 mRNA in the basal layer of the epidermis and mRNAs for IGFBP-4, and IGFBP-5 found throughout the dermis. mRNAs for IGFBP-1 and -6 were not identified in human skin. These studies demonstrate specific localization of IGFBP mRNAs in adult human skin, suggesting that each IGFBP may play a specific role in targeting IGF-I to its receptor on responsive cells and, ultimately, in modulation of IGF-I action in skin.