Aromatase in bone cell: Association with osteoporosis in postmenopausal women

Abstract To clarify the possible action of adrenal androgen on bone cell, the existence, characteristics and regulation of aromatase in human osteoblast-like osteosarcoma cells (HOS) and primary cultured osteoblast-like cells from normal human bones (HO) were examined in this study. Significant positive correlation between bone mineral density (BMD) and serum dehydroepiandrosterone sulfate (DHEA-S) was found in 120 postmenopausal women (51–99 years old) but no correlation was seen between BMD and serum estradiol (E 2 ). In subset analysis, strongly positive correlation of serum DHEA-S and estrone (E 1 ) with BMD was observed in postmenopausal women aged less than 69 years old. Administration of DHEA to ovariectomized rat significantly increased BMD and decreased relative osteoid volume in femur. These in vivo findings strongly suggested that serum adrenal androgen may be converted to estrogen in peripheral organ, especially, osteoblast and be important steroids to maintain BMD. [ 3 H]DHEA was converted to [ 3 H]androstenedione and [ 3 H]androstenedione to [ 3 H]estrone in primary cultured human osteoblast. Osteoblast-like cells showed aromatase activity, and an apparent K m and the V max were 4.74 ± 0.78 nM (mean ± SD, n = 3) and 0.83 ± 0.79 fmol/mg protein/h for HOS, and 4.6 ± 2.9 nM and 279 ± 299 fmol/mg protein/h (mean ± SD, n = 19) for HO, respectively. The aromatase activity was significantly increased by dexamethasone in a dose-dependent manner. Reverse transcription-polymerase chain reaction analysis revealed that dexamethasone increased the transcript of P 450 AROM gene. Osteoblast-specific promoters were also determined. Dexamethasone and 1α,25-dihydroxyvitamin D 3 synergistically enhanced aromatase activity and P 450 AROM mRNA expression. These results demonstrate that adrenal androgen, DHEA, is converted to E 1 in osteoblast by P 450 AROM which is positively regulated by glucocorticoid and 1α,25-dihydroxyvitamin D 3 and important to maintain BMD in the 6 to 7th decade, after menopause.