Regulation of proliferation of rat cartilage and bone by sex steroid hormones.

Abstract We have demonstrated previously that 17β-estradiol (E 2 ) stimulates proliferation of skeletal tissues, both in vivo and in vitro , as measured by increased DNA synthesis and creatine kinase (CK) specific activity. The effect of E 2 on bone is sex specific. E 2 is active only in females and androgens only in males. By contrast, in cartilage of both sexes, dihydrotestosterone (DHT) as well as E 2 stimulates CK specific activity and DNA synthesis. In bone, we find that sex steroids stimulate skeletal cell proliferation in gonadectomized as well as in immature rats. Ovariectomized (OVX) rats, between 1 and 4 weeks after surgery, show stimulation of CK by E 2 . The basal activity and response of CK changes with the varying endogenous levels of E 2 in cycling rats, in which the highest basal activity is at proestrus and estrus and the highest response is in diestrus. In rats of all ages tested, both the basal and stimulated specific activity of CK is higher in diaphysis and epiphysis than in the uterus, or in the adipose tissue adjacent to the uterus, which has a response similar to that of the uterus itself. The effect of E 2 in vivo , and in chrondroblasts and osteoblasts in vitro , is inhibited by high levels of the antiestrogen tamoxifen which, by itself, in similar high concentrations, shows stimulatory effects. In addition to the sex steroids, skeletal cells are also stimulated by secosteroid and peptide calciotrophic hormones. The interactions of the sex steroids and the other calciotrophic hormones. These results provide the first steps towards understanding the regulation of bone cell proliferation and growth by the concerted action of a variety of hormones and growth factors.