IGF-1 STIMULATES SYNTHESIS OF UNDERSULFATED PROTEOGLYCANS AND OF HYALURONIC-ACID BY PERITUBULAR CELLS FROM IMMATURE RAT TESTIS

The exposure of confluent peritubular (PT) cells from immature rat tes tis to insulin-like growth factor-1 (IGF-1) induced a time and dose-de pendent increase of [S-35]-sulfate and [H-3]-D-glucosamine incorporati ons in newly synthesized proteoglycans (PG). This increased content of PG was the result of an enhancement of PG synthesis rather than a dec reased rate of degradation. IGF-1 had no effect on the molecular weigh t of synthesized PG nor on the nature and distribution of the constitu tive glycosaminoglycan chains, both in medium and in cell layer. The s timulation of PG synthesis by IGF-1 appeared to be due, at least parti ally, to an increase of glycosylation processes. IGF-1 effect was medi ated by the classical tyrosine kinase signalling process, since IGF-1 action on PG synthesis was abolished by genistein and tyrphostin A9, t wo well known tyrosine kinase inhibitors. The increase of PG synthesis was accompanied with an undersulfation of constitutive glycosaminogly can (GAG) chains (chondroitin sulfate and heparan sulfate chains) sinc e the [S-35]/[H-3] ratio was reduced by about 20-25% in presence of IG F-1, Although the mechanism of hyaluronic acid synthesis was completel y different from those of other GAG, IGF-1 also dramatically enhanced its production by PT cells. (C) 1997 Elsevier Science B.V.