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Characterization of Aromatase and 17β‐Hydroxysteroid Dehydrogenase Expression in Rat Osteoblastic Cells
Author(s) -
Eyre Louise J.,
Bland Rosemary,
Bujalska Iwona J.,
Sheppard Michael C.,
Stewart Paul M.,
Hewison Martin
Publication year - 1998
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1998.13.6.996
Subject(s) - aromatase , androstenedione , medicine , endocrinology , testosterone (patch) , cell culture , chemistry , estrone , bone cell , estrogen , osteoblast , biology , hormone , androgen , biochemistry , in vitro , genetics , cancer , breast cancer
Postmenopausal loss of 17β‐estradiol (E 2 ) in women is associated with decreased bone mineral density and increased susceptibility to osteoporotic bone fracture. These changes in bone status are assumed to be due to circulating levels of the hormone; therapeutic replacement of E 2 can alleviate the bone disease. However, recent reports have shown that human osteoblastic (OB) cells are able to synthesize estrogens locally, via expression of the enzyme aromatase. In this study, we have characterized the expression and activity of aromatase and 17β‐hydroxysteroid dehydrogenase (17β‐HSD) in rat OB cell lines. Aromatase activity in ROS 17/2.8, ROS 25/1, and UMR 106 cells was similar to that shown in human OB cells, with the highest levels of activity observed in the more differentiated ROS 17/2.8 cells (V max = 45 pmol/h/mg of protein). The rat OB cells also showed 17β‐HSD activity, with the predominant metabolism in all three cell lines being estrone (E 1 ) to E 2 . As with aromatase, the highest activity was observed in ROS 17/2.8 cells ( V max = 800 pmol/h/mg of protein). Northern analyses indicated the variable presence of transcripts corresponding to the type 1, 2, 3, and 4 isoforms of 17β‐HSD. Further analysis of androstenedione metabolism indicated that the net effect of aromatase and 17β‐HSD activity varied with cell type and culture treatment. All three OB cell lines were able to synthesize E 1 , E 2 , and testosterone from androstenedione, although activity varied between OB cell types. Regulatory effects were observed with 1,25‐dihydroxyvitamin D 3 (positive) and dexamethasone (negative). These data suggest that local synthesis of sex hormones is an important function of OB cells and may play a key role in the modulation of bone turnover independent of circulating hormone concentrations.