Progesterone stimulates proliferation and differentiation of osteoprogenitor cells in bone cell populations derived from adult female but not from adult male rats.

We examined the effects of the synthetic glucocorticoid dexamethasone (Dex) and of the sex steroids progesterone (Prog) and testosterone (Testo) on proliferation and differentiation of progenitors for osteoblasts, adipocytes, and macrophages in cell populations derived from lumbar vertebrae of adult male and female rats. To assay for these progenitors, we used a previously described colony assay, where progenitors are identified by the appearance of colonies of the differentiated phenotype in long term cultures of cell populations containing these progenitors. In cell populations derived from both males and females, Dex (10(-9)-10(-6) mol/L) induced a similar dose-dependent increase in the number of osteoblast colonies (bone nodules), colonies of alkaline phosphatase (AP)-positive cells, adipocyte colonies and macrophage colonies (ED2-positive cells). Prog (10(-8)-10(-5) mol/L), on the other hand, increased bone nodule formation in female-derived populations but not in male-derived populations. Maximal stimulation was seen at 10(-5) mol/L. 17 beta-Estradiol (E2) enhanced the Prog-induced increase in the number of bone nodules in a dose-related fashion. Maximal stimulation was seen at 10(-8) mol/L E2. E2 (10(-9)-10(-6) mol/L) had no effect on Dex-induced bone nodule formation, indicating that the effect is specific for Prog-induced stimulation of bone nodule formation. Prog also caused a dose-dependent increase in the number of colonies of AP-positive cells. Interestingly, the effect of Prog on the number of AP-positive colonies was the same in populations derived from both sexes. Prog-induced stimulation of adipocyte and macrophage development in female-derived populations was significantly greater than that in male-derived populations. Testo (10(-9)-10(-5) mol/L) had no effect on any of the parameters evaluated in populations derived from either males or females. These observations demonstrate that the effect of Prog on proliferation and differentiation of progenitors for osteoblasts, adipocytes, and macrophages in cell populations derived from lumbar vertebrae of adult male or female rats is sex-dependent and is seen either only (bone nodule formation) or more pronounced (adipocyte and macrophage development) in female-derived populations.