Aromatase in bone: Roles of Vitamin D3 and androgens

Toshihiko Yanase, Shizu Suzuki, Kiminobu Goto, Masatoshi Nomura, Taijiro Okabe, Ryoichi Takayanagi, Hajime Nawata

研究成果: ジャーナルへの寄稿学術誌査読

59 被引用数 (Scopus)


We have mainly focused on the regulatory mechanism of cytochrome P450 aromatize in bone cells. Our previous study demonstrated a strong positive correlation of serum dehydroepiandrosterone sulfate (DHEA-S) and estrone (E1) with BMD in postmenopausal women but no correlation between serum estradiol (E2) and BMD in the same group. In addition, administration of DHEA to ovariectomized rat significantly increased BMD. These in vivo findings strongly suggested that circulating adrenal androgen may be converted to estrogen in osteoblast and may contribute to BMD maintenance. Actually, in cultured human osteoblast cells, DHEA was found to convert to androstenedione by 3β-hydroxysteroid dehydrogenase (3β-HSD) activity and then androstenedione to estrone through the apparent aromatase activity. The aromatase activity in cultured human osteoblast cells was significantly increased by dexamethasone (DEX). Interestingly, DEX and 1α,25- dihydroxyvitamin D3 (VD3) synergistically enhanced aromatase activity as well as P450arom mRNA expression. A little stronger induction of aromatase activity by DEX and VD3 was observed in cultured human fibroblasts. The increase of the aromatase activity by DEX and VD3 was accompanied with the increase of luciferase activity of fibroblast cells transfected with Exon 1b-promoter-luciferase construct, but not of osteoblasts transfected with the same construct, suggesting a different regulatory mechanism of aromatase by DEX and 1α,25-dihydroxyvitamin D 3 (VD3) between these two cells despite the same promotor usuage. In human bone cells, intracrine mechanism through aromatase activity, together with a positive regulation of aromatase activity by glucocorticoid and VD3, may contribute to the local production of estrogens, thus leading to protective effect against osteoporosis especially after menopause. The effect of sex steroids (estrogen versus testosterone) in bone remodeling was also briefly reviewed based on several recent findings in this field.

ジャーナルJournal of Steroid Biochemistry and Molecular Biology
出版ステータス出版済み - 9月 2003

!!!All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 分子医療
  • 分子生物学
  • 内分泌学
  • 臨床生化学
  • 細胞生物学


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