Dehydroepiandrosterone (DHEA) as a possible source for estrogen formation in bone cells: correlation between bone mineral density and serum DHEA-sulfate concentration in postmenopausal women, and the presence of aromatase to be enhanced by 1,25-dihydroxyvitamin D3 in human osteoblasts

Mech Ageing Dev. 2002 Apr 30;123(8):1107-14. doi: 10.1016/s0047-6374(01)00394-3.


A 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. In subset analysis, strong positive correlation of serum DHEA-S and estrone with BMD was observed in postmenopausal women aged less than 69 years old. To study a possible role of DHEA-S in preventing osteoporosis, we characterized aromatase activity converting androgens to estrogens in human osteoblasts, because postmenopausal women maintain considerable levels of adrenal androgens. Glucocorticoids at 10(-9) to 10(-7) M induced transiently the expression of and the enzymatic activity of aromatase cytochrome P450 (P450AROM) in primary cultured osteoblasts. 1,25-Dihydroxyvitamin D3 (1,25-(OH)(2)D(3)) alone did not induce the aromatase activity, but enhanced and maintained the glucocorticoid-induced P450AROM gene expression. Analysis of the activity of P450AROM gene 1b (I.4) promoter, which is used dominantly in human osteoblasts, indicated that the region from -888 bp to -500 bp, which does not contain a typical vitamin D responsive element, is responsible for the enhancing effect of 1,25-(OH)(2)D(3). These results may suggest that adrenal androgen, DHEA, is converted to estrone in osteoblast by P450AROM, which is positively regulated by glucocorticoid and 1,25-(OH)(2)D(3), and is important in maintaining BMD in the sixth to the seventh decade, after menopause.

MeSH terms

  • 24,25-Dihydroxyvitamin D 3 / pharmacology
  • Aged
  • Aged, 80 and over
  • Aromatase / genetics
  • Aromatase / metabolism*
  • Bone Density
  • Calcitriol / pharmacology*
  • Cells, Cultured
  • Dehydroepiandrosterone / blood
  • Dehydroepiandrosterone / metabolism*
  • Dehydroepiandrosterone Sulfate / blood*
  • Dexamethasone / pharmacology
  • Estradiol / pharmacology
  • Estrogens / metabolism*
  • Female
  • Femur / cytology
  • Humans
  • Middle Aged
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Postmenopause / metabolism*
  • Promoter Regions, Genetic
  • Tretinoin / pharmacology


  • Estrogens
  • 24,25-Dihydroxyvitamin D 3
  • Dehydroepiandrosterone
  • Estradiol
  • Tretinoin
  • Dehydroepiandrosterone Sulfate
  • Dexamethasone
  • Aromatase
  • Calcitriol