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Estradiol formation by human osteoblasts via multiple pathways: Relation with osteoblast function
Author(s) -
Janssen J.M.M.F.,
Bland R.,
Hewison M.,
Coughtrie M.W.H.,
Sharp S.,
Arts J.,
Pols H.A.P.,
van Leeuwen J.P.T.M.
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19991201)75:3<528::aid-jcb16>3.0.co;2-3
Subject(s) - estrone , aromatase , androstenedione , endocrinology , medicine , estrogen , chemistry , osteoblast , testosterone (patch) , sulfatase , enzyme , biology , in vitro , biochemistry , androgen , hormone , cancer , breast cancer
The importance of estrogens in bone metabolism is illustrated by the accelerated bone loss and increase in osteoporotic fractures associated with postmenopausal estrogen deficiency. In this study, the expression and activity of the enzymes involved in estrogen metabolism in human osteoblastic cells were investigated in relation to differentiation of these cells. PCR reactions using mRNA from an in vitro differentiating human cell line (SV‐HFO) were performed to assess mRNA expression of the enzymes aromatase, different subtypes of 17β‐hydroxysteroid dehydrogenase (17β‐HSD), and steroid sulfatase. Aromatase, sulfatase, and 17β‐HSD type 2 and 4 were found to be expressed throughout differentiation. Expression of 17β‐HSD type 3, however, was relatively weak, except for early time points in differentiation. Type 1 17β‐HSD expression was not detected. Aromatase activity decreased during differentiation, as was demonstrated by the conversion of androstenedione (A) and testosterone (T) into estrone (E 1 ) and estradiol (E 2 ), respectively. The 17β‐HSD isozymes catalysing a reductive reaction convert androstenedione and estrone into testosterone and estradiol, respectively. Their activity declined with differentiation. Analysis of 17β‐HSD activity indicated both oxidative (E 2 to E 1 ; T to A) and reductive (E 1 to E 2 ; A to T) metabolism at all stages of osteoblast differentiation. Both activities declined as cells moved toward a differentiating mineralizing phenotype. However, the oxidative reaction was increasingly in favor of the reductive reaction at all times during differentiation. Sulfatase activity, as demonstrated by the conversion of estrone‐sulfate into estrone, was constant during differentiation. In conclusion, we have demonstrated that all enzymes necessary for estrogen metabolism are expressed and biologically active in differentiating human osteoblasts. The activity of aromatase and 17β‐HSD was found to be dependent on the stage of cell differentiation. In addition, human osteoblasts effectively convert estradiol into estrone. The efficacy of osteoblasts to synthesize estradiol may determine the ultimate change in rate of bone turnover after menopause, as well as the development of osteoporosis. Moreover, the enzymes involved in the metabolism of estradiol may form a target for intervention. J. Cell. Biochem. 75:528–537, 1999. © 1999 Wiley‐Liss, Inc.