Cultured human fibroblasts secrete insulin-like growth factor IA prohormone.

Nucleotide sequencing of the two known cDNAs encoding human insulin-like growth factor I (IGF-I) predicts the existence of two different prohormone forms of IGF-I. The E peptide regions extend the carboxy-terminus of IGF-I by either an additional 35 (IGF-IA) or 77 (IGF-IB) amino acids. With a specific and sensitive RIA employing an antiserum directed against a synthetic peptide that is unique to the E peptide region of IGF-IA prohormone (EIA), we have identified EIA-immunoreactive material in the conditioned medium of fetal and postnatal human fibroblasts in culture. Incubation of postnatal human fibroblasts with GH increased specific immunoreactive EIA secretion 2- to 3-fold. There was no immunologically detectable 7.5K IGF-I or IGF-II peptide in acid-chromatographed human fibroblast-conditioned medium under either basal or GH-stimulated conditions. Acid chromatography of human fibroblast-conditioned medium on Sephadex G-75 revealed a single elution peak of EIA immunoreactivity corresponding to a mol wt of 9-17 K. With neutral chromatography, EIA immunoreactivity eluted at 25-38K mol wt. These data suggest that the E peptide region of IGF-IA is translated and released as part of the prohormone form in cultured human fibroblasts, and that the levels of this prohormone are regulated by GH.