Aromatase in bone cell: association with osteoporosis in postmenopausal women.
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 (E2). In subset analysis, strongly positive correlation of serum DHEA-S and estrone (E1) 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. [3H]DHEA was converted to [3H]androstenedione and [3H]androstenedione to [3H]estrone in primary cultured human osteoblast. Osteoblast-like cells showed aromatase activity, and an apparent Km and the Vmax 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 P450AROM gene. Osteoblast-specific promoters were also determined. Dexamethasone and 1 alpha,25-dihydroxyvitamin D3 synergistically enhanced aromatase activity and P450AROM mRNA expression. These results demonstrate that adrenal androgen, DHEA, is converted to E1 in osteoblast by P450AROM which is positively regulated by glucocorticoid and 1 alpha,25-dihydroxyvitamin D3 and important to maintain BMD in the 6 to 7th decade, after menopause.
Nawata
H
H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Tanaka
S
S
Tanaka
S
S
Takayanagi
R
R
Sakai
Y
Y
Yanase
T
T
Ikuyama
S
S
Haji
M
M
D000368:Aged; D000735:Androstenedione / Q000494:pharmacology; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001483:Base Sequence; D015519:Bone Density; D001842:Bone and Bones / Q000201:enzymology*; D002117:Calcitriol / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000201:enzymology; D010024:Osteoporosis / Q000201:enzymology*; D012516:Osteosarcoma / Q000201:enzymology; D010052:Ovariectomy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013739:Testosterone / Q000494:pharmacology
D017931:DNA Primers; D012333:RNA, Messenger; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D001141:Aromatase; D002117:Calcitriol