COMPARISON OF THE ACTION OF 17-BETA-ESTRADIOL AND PROGESTINS WITH INSULIN-LIKE GROWTH FACTORS-I -II AND TRANSFORMING GROWTH-FACTOR-BETA-1 ON THE GROWTH OF NORMAL ADULT HUMAN BONE-FORMING CELLS/

Endogenous growth factors may be involved in the prevention of bone lo ss by estrogen and progestins in postmenopausal women. The present stu dy was performed to compare the action of estrogen/progestins on bone- derived cells with the effects of exogenously added purified growth fa ctors. Human osteoblast-like (HOB) cells were incubated with 17 beta-e stradiol (E(2)), progesterone (P), dydrogesterone (DD), 20 alpha-dihyd roxydydrogesterone (DHD), with and without the growth factors, insulin -like growth factors-I/-II(IGF-U-II) or transforming growth factor-bet a type 1 (TGF-beta 1) for 24 h under serum-free conditions. Cell growt h and DNA synthesis were assessed by spectophotometrical analysis of t otal cell number and immunochemical detection of BrdU incorporation, r espectively. Compared with the sex steroids, incubation of the cells w ith ICE-I or TGF-beta 1 resulted in at least a two-fold increase of to tal HOB cell numbers. No difference in stimulating HOB growth was obse rved between IGF-II and the female sex steroids E(2) and P. Combining IGF-I/-II or TGF-beta 1 with either E(2) or P did not result in a sign ificantly further increase in the human osteoblast-like cell growth. I n conclusion, the bone anabolic growth factors, IGF-I and TGF-beta 1, may be more important regulators of osteoblast proliferation than the female sex steroids. An interaction of estrogen/gestagens with the gro wth factors IGF-I/-II or TGF-beta 1 was not evident from the growth of human bone-forming cells in short-term cultures.