AROMATASE IN BONE CELL - ASSOCIATION WITH OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN

To clarify the possible action of adrenal androgen on bone cell, the e xistence, characteristics and regulation of aromatase in human osteobl ast-like osteosarcoma cells (HOS) and primary cultured osteoblast-like cells from normal human bones (NO) were examined in this study. Signi ficant positive correlation between bone mineral density (BMD) and ser um dehydroepiandrosterone sulfate (DHEA-S) was found in 120 postmenopa usal women (51-99 years old) but no correlation was seen between BMD a nd serum estradiol (E(2)). In subset analysis, strongly positive corre lation of serum DHEA-S and estrone (E(1)) with BMD was observed in pos tmenopausal women aged less than 69 years old. Administration of DHEA to ovariectomized rat significantly increased BMD and decreased relati ve 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 B MD. [H-3]DHEA was converted to [H-3]androstenedione and [H-3]androsten edione to [H-3]estrone in primary cultured human osteoblast. Osteoblas t-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 prote in/h (mean +/- SD, n = 19) for HO, respectively. The aromatase activit y was significantly increased by dexamethasone in a dose-dependent man ner. Reverse transcription-polymerase chain reaction analysis revealed that dexamethasone increased the transcript of P450(AROM) gene. Osteo blast-specific promoters were also determined. Dexamethasone and 1 alp ha,25-dihydroxyvitamin D-3 synergistically enhanced aromatase activity and P450(AROM), mRNA expression. These results demonstrate that adren al androgen, DHEA, is converted to E(1) in osteoblast by P450(AROM) wh ich is positively regulated by glucocorticoid and 1 alpha,25-dihydroxy vitamin D-3 and important to maintain BMD in the 6 to 7th decade, afte r menopause.