Contribution of circulating IGF-I to wound repair in GH-treated rats.

Systemic administration of growth hormone (GH) stimulates granulation tissue formation, increases collagen deposition, improves the breaking strength of incisional wounds, and decreases donor-site healing times in burn patients. The possible role for circulating IGF-I in mediating this effect of growth hormone has not been investigated. To assess the relative effects of systemic IGF-I and GH on dermal repair, incisional wounds were created on the backs of male Sprague-Dawley rats treated with GH, or IGF-I or a combination of GH and IGF-I. After 7 days of treatment, wound strips were taken for wound strength and immunohistochemical analysis. Uninjured skin and liver samples were collected for mRNA analysis and plasma samples were taken at the completion of the experiment to determine circulating IGF-I levels. Increased circulating IGF-I levels and increased weight gain were observed only in the IGF-I and IGF-I+GH treatment groups, although steady-state igf-I levels were not altered in liver and uninjured skin after 7 days in any treatment group. IGF-I treatment had no positive effects on wound repair. Wound strength was increased with GH treatment only and associated with an increase in the intensity of IGF-I immunostaining in the granulation tissue of GH-treated animals. In line with the wound strength data, co-administration of IGF-I resulted in the decreased intensity of IGF-I immunostaining. We conclude that the GH-stimulated increase in wound strength is not mediated via endocrine-derived IGF-I and that only locally produced IGF-I acting in an autocrine or paracrine fashion contributes to the regulation of the wound repair process.