Multiple hormones stimulate the production of somatomedin by cultured human fibroblasts.

Abstract

Although immunoreactive somatomedin (IR-SM) secretion by cultured human fibroblasts has been reported, the hormonal control of IR-SM production is not well defined. This study concerns the effects of several hormones and growth factors on IR-SM production by cultured human fibroblasts. Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) had concentration-dependent stimulatory effects on IR-SM production when added to confluent quiescent cultures. When PDGF, FGF, macrophage growth factor (MGF), or epidermal growth factor (EGF) was added transiently for 5 h and the cells subsequently incubated in SM-C deficient, platelet-poor plasma (SM-C-deficient PPP), persistent stimulation of IR-SM production occurred. In contrast, transient exposure to other known stimuli of IR-SM production, such as human GH, T4, and insulin, resulted in no stimulation. Continuous exposure of quiescent, high density fibroblast cultures to EGF, insulin, hydrocortisone, or T4 incubated in the presence of serum-free medium alone resulted in no significant stimulation. During simultaneous incubation with PDGF and SM-C-deficient PPP, however, hydrocortisone, T4, EGF, and insulin produced concentration-dependent increases in IR-SM production. After transient exposure to PDGF, only hydrocortisone and T4 were stimulatory in the presence of SM-C-deficient PPP. We conclude that competence factors, such as PDGF and FGF, are potent stimuli of IR-SM production in the presence of serum-free medium, and that this hormonal signal can be remembered by the cell even after withdrawal of the growth factor. In contrast, progression factors, such as hydrocortisone, T4, and insulin, are effective only in nonquiescent cells. EGF and insulin require simultaneous incubation with PDGF. The PDGF-stimulated cell, therefore, responded differently to hormonal stimuli of IR-SM production than did the quiescent cell.