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Direct Action of Naturally Occurring Estrogen Metabolites on Human Osteoblastic Cells
Author(s) -
Robinson John A.,
Waters Katrina M.,
Turner Russell T.,
Spelsberg Thomas C.
Publication year - 2000
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.2000.15.3.499
Subject(s) - endocrinology , medicine , estrogen , estrogen receptor , osteoblast , osteocalcin , estrogen receptor alpha , estrogen receptor beta , biology , alkaline phosphatase , in vitro , biochemistry , cancer , breast cancer , enzyme
This article describes experiments that were performed to examine the direct action of estrogen metabolites on cultured human osteoblast cells. The human fetal osteoblastic cell line, hFOB/ER9, which expresses high levels of the estrogen receptor (ER) alpha, was used to examine the direct effects of 16α‐hydroxyestrone (16α‐OHE 1 ) and 2‐hydroxyestrone (2‐OHE 1 ) on osteoblast differentiation. The 16α‐OHE 1 caused a decrease in osteocalcin (OC) secretion to a maximum of 40% of control values (vehicle‐treated cells) at 10 −7 M. Alkaline phosphatase (AP) activity was significantly induced at 10 −7 M 16α‐OHE 1 with greater than 500% of control at 10 −6 M 16α‐OHE 1 . Finally, AP steady‐state messenger RNA (mRNA) levels were increased within 24 h of 16α‐OHE 1 treatment. In contrast to 16α‐OHE 1 , 2‐OHE 1 had no effects on the secretion of OC, AP activity, or AP gene expression. The 2‐OHE 1 also did not display any antiestrogen activity because treatment in combination with 17β‐estradiol (E 2 ) and 16α‐OHE 1 had no significant effect on the reduction in OC secretion or induction of AP activity. Similar to E 2 , 16α‐OHE 1 stimulated the expression of an early response gene, a TGF‐β inducible early gene, designated TIEG, as early as 60 minutes after treatment, whereas treatment with 2‐OHE 1 displayed no effect. Support that the 16α‐OHE 1 regulation of these osteoblasts (OB) markers was mediated through the ER is shown by the fact that the estrogen antagonist ICI 182,780 abrogated these effects. These data suggest that 16α‐OHE 1 is a potent estrogen agonist on human osteoblastic hOB/ER9 cells. In contrast, 2‐OHE 1 displayed no estrogenic or antiestrogenic activity in this human osteoblast cell model.