EFFECTS OF ANDROGENS ON SUBPOPULATIONS OF THE HUMAN OSTEOSARCOMA CELL-LINE SAOS2

Previously, we showed that androgens stimulate murine and human osteob last-like cell proliferation and differentiation by mechanisms involvi ng increased responses to mitogenic growth factors (GF) and increased GF production. To explain this dual action of androgens on primary ost eoblastic cell populations we advanced the hypothesis that androgens e xert differential effects on osteoblastic subpopulations. We subcloned a human osteosarcoma cell line (SaOS2) into subpopulations expressing high (HAS) and low (LAS) levels of alkaline phosphatase (ALP). The ob tained subclones differed significantly in their ALP production and ex pressed a high and low ALP phenotype, respectively, for the entire exp erimental period. Dihydrotestosterone (DHT) increased specific ALP act ivity and type-I procollagen peptide secretion in both HAS and LAS. DH T pretreatment enhanced the mitogenic action of basic fibroblast growt h factor (bFGF) and insulinlike growth factor 2 (IGF2) only in HAS. Th e enhanced mitogenic effect of IGF2 in HAS after DHT pretreatment was associated with increased IGF2-receptor mRNA levels. Therefore, we con clude that androgens exert their osteoanabolic action (1) by stimulati ng differentiated functions of osteoblastic cells with a high and a lo w ALP phenotype, and (2) via increased growth factor receptor expressi on and thereby enhancing mitogenic growth factor responses only in HAS .