Progesterone-responsive Osteoprogenitors Are Regulated by Estrogen and Distinct from Glucocorticoid-responsive Osteoprogenitors

Postmenopausal bone loss is clearly associated with a deficiency of sex steroids (1), and estrogen replacement therapy prevents it (2). Progesterone (Prog) deficiency could also be a factor, and Prog replacement therapy has indeed been shown to prevent postmenopausal bone loss and bone loss associated with ovarian dysfunction (3). In the osteoprogenitor assay system that we developed, morphologically recognizable osteoblasts and bone nodules appear in long-term rat calvaria or adult rat vertebral cell cultures at predictable and reproducible periods after plating (4-7). The uniqueness of this system is that it allows one to identify osteoprogenitors on the basis of a clearly identifiable end point, i.e. bone formation, and thus is able to identify populations of progenitors that could be heterogeneous for several other characteristics (for example, surface antigens, receptors). In our studies of these osteoprogenitors, we have discovered that, in addition to the previously found dexamethasone (Dex)-dependent and Dexindependent classes of progenitors found in calvaria of fetal rats (4), a new class of Prog-responsive progenitors was present in female-derived but not in male-derived adult cell populations (5,6). The main aim of the present study was to investigate the changes with aging of the characteristics and the sex steroid regulation of proliferation and differentiation of these osteoprogenitors and whether Progand Dexresponsive osteoprogenitors are two different and distinct progenitor populations.