Recent clinical studies suggest that progesterone may be involved in the regulation of bone turnover and could promote bone formation. This study was undertaken to evaluate whether progesterone and promegestone (a 19 nor-PG derivative) may have a direct effect on human bone cells and, if so, whether growth factor production could be involved in promoting this effect. The osteosarcoma cell line TE85 and untransformed normal human osteoblastic cells derived from iliac crest were used as in vitro model systems. Progesterone and promegestone were found to significantly increase [3H]thymidine incorporation in TE85 cells in a dose-dependent manner at concentrations ranging from 10(-12) to 10(-8) mol/l after four days of cultivation (p less than 0.01, ANOVA). Consistent with this response in the TE85 cells, progesterone and promegestone increased cell number in human osteoblastic cells after six days of treatment (p less than 0.05, ANOVA). To determine whether this effect on cell proliferation was mediated by the insulin-like growth factor (IGF) regulatory system, the levels of IGF-1, IGF-2 and IGF binding protein (IGFBP) were measured in the conditioned media of both TE85 and human osteoblast cells. While no significant changes in IGF-1 levels were found in the conditioned media of progesterone and promegestone treated cultures, progesterone and promegestone at the concentration of 5 nmol/l significantly increased IGF-2 levels 2.4 and 1.5-fold respectively, at 48 h in the conditioned medium of TE85 cells as compared to control. Similarly, a 4.1 and 1.9-fold increase in IGF-2 levels was found upon treatment with progesterone and promegestone in human osteoblastic cells.(ABSTRACT TRUNCATED AT 250 WORDS)