LOCAL ESTRADIOL METABOLISM IN OSTEOBLAST-LIKE AND OSTEOCLAST-LIKE CELLS

Bone is an estradiol-responsive tissue. Estrogen withdrawal during the menopause causes loss of bone mass and clinically relevant osteoporos is in a third of all women. Sufficient or impaired local production, a s well as degradation of estradiol in cells present in the bone microe nvironment might be an important mechanism of rescue or might contribu te to the development of osteoporosis, respectively. We therefore inve stigated aromatase and 17 beta-hydroxysteroid dehydrogenase type IV (I 7 beta-HSD IV) expression in osteoblast-and osteoclast-like cells. Aro matase mRNA was increasingly expressed in myeloid THP 1 cells differen tiated along the monocyte/phagocyte pathway exploiting vitamin D and e ither granulocyte-macrophage-stimulating factor (GMCSF) or macrophage- stimulating factor ((MCSF). In long-term cultures, when sequentially e xposed to vitamin D (days 0-21) and GMCSF (days 5-10) and plated on co llagen, the amount of expression of aromatase mRNA steadily increased along with the increasing expression of osteopontin mRNA, alpha nu int egrin mRNA, c-fms (MCSF-receptor) mRNA and multinucleated cells develo ping. The conversion of estradiol from testosterone (10(-7) M/l) in th e supernatants of dishes mirrored changes in aromatase mRNA expression and by day 21 rose to 30,000 ng/10(7) cells/24 h. 17 beta-HSD IV mRNA expression was abundant in undifferentiated THP 1 cells and was decre ased to approximately 50% by day 21. Unstimulated SV-40 immortalized f etal osteoblasts did not express aromatase mRNA, but the expression wa s stimulated by the addition of the phorbol ester phorbol myristate ac etate (PMA). Unstimulated osteoblasts from primary cultures did not ex press aromatase mRNA. Osteoblast-like osteosarcoma cells MG 63 express ed faint levels of aromatase mRNA in contrast to the osteosarcoma cell line HOS 58. 17 beta-HSD IV mRNA was expressed in fetal osteoblasts a s well as in osteoblasts from primary culture, MG 63 and HOS 58 cells. In summary, we can show the expression of estradiol metabolizing enzy mes in cells which are present in the bone microenvironment. Impaired aromatase expression and/or enhanced expression of I7 beta-HSD IV may contribute to the pathogenesis of osteoporosis. (C) 1997 Elsevier Scie nce Ltd.