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Cultured Human Fibroblasts Secrete Insulin-Like Growth Factor IA Prohormone^*

Department of Pediatrics, Stanford University Stanford, California 94305

Address requests for reprints to: Dr. Cheryl Conover, Endocrine Research Unit, Room 5–164 West Joseph Building, Mayo Clinic, Rochester, Minnesota 55905.

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 (ElA), 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.

^* This work was supported in part by NIH Grant DK-24085.

Received November 7, 1988.

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