TY - JOUR
T1 - Estrogen effects on insulin-like growth factor gene expression in a human osteoblastic cell line with high levels of estrogen receptor
AU - Kassem, M.
AU - Okazaki, R.
AU - Harris, S. A.
AU - Spelsberg, T. C.
AU - Conover, C. A.
AU - Riggs, B. L.
PY - 1998
Y1 - 1998
N2 - Insulin-like growth factors (IGF)-I and IGF-II are produced by osteoblasts and are important paracrine/autocrine regulators of osteoblast proliferation and differentiation. Estrogen has been reported to increase gene expression of IGF-I in rodent osteoblasts. However, because species differences have been demonstrated in expression of various aspects of the IGF system in bone cells, it is not known whether this action also occurs in human osteoblasts. Thus, we assessed the effects of estrogen treatment on IGF-I and IGF-II gene expression in vitro in a recently developed human fetal osteoblast cell line that has high levels of estrogen receptors. As assessed by a quantitative reverse transcriptase-polymerase chain reaction method, treatment of hFOB/ER9 cells with 17β-estradiol (E2) increased steady state levels of IGF-I mRNA in a time- and dose- dependent fashion with a maximal increase of 319% ± 33% (P < 0.01) of control occurring after treatment with 10-7 M E2 for 48 hours. In contrast, E2 did not alter steady state levels of 1GF-II mRNA. The pure (type 2) antiestrogens ICI 182,780 (10-7 M) and ICI 164,384 (10-6 M) blocked the E2- induced increase in IGF-I mRNA levels. Interestingly, 4-hydroxytamoxifen (10-7 M), a documented pure antiestrogen in reproductive tissues, also increased IGF-I mRNA to levels similar to those observed in E2-treated cells. Since E2 was shown to mediate its effects on some target genes through a cAMP- dependent pathway, we studied the interaction between E2 and agents that are known to increase intracellular cAMP. Forskolin (10-8 M) and dibutyryl cAMP (10-3 M) increased IGF-I mRNA levels sixfold, and cotreatment with E2 did not affect these changes, consistent with a possible mediation of the estrogen effect on IGF-I gene expression by cAMP. We conclude that in human osteoblastic cells, the IGF-I gene is a target for estrogen action, suggesting that IGF-I may mediate part of the effects of estrogen in human bone.
AB - Insulin-like growth factors (IGF)-I and IGF-II are produced by osteoblasts and are important paracrine/autocrine regulators of osteoblast proliferation and differentiation. Estrogen has been reported to increase gene expression of IGF-I in rodent osteoblasts. However, because species differences have been demonstrated in expression of various aspects of the IGF system in bone cells, it is not known whether this action also occurs in human osteoblasts. Thus, we assessed the effects of estrogen treatment on IGF-I and IGF-II gene expression in vitro in a recently developed human fetal osteoblast cell line that has high levels of estrogen receptors. As assessed by a quantitative reverse transcriptase-polymerase chain reaction method, treatment of hFOB/ER9 cells with 17β-estradiol (E2) increased steady state levels of IGF-I mRNA in a time- and dose- dependent fashion with a maximal increase of 319% ± 33% (P < 0.01) of control occurring after treatment with 10-7 M E2 for 48 hours. In contrast, E2 did not alter steady state levels of 1GF-II mRNA. The pure (type 2) antiestrogens ICI 182,780 (10-7 M) and ICI 164,384 (10-6 M) blocked the E2- induced increase in IGF-I mRNA levels. Interestingly, 4-hydroxytamoxifen (10-7 M), a documented pure antiestrogen in reproductive tissues, also increased IGF-I mRNA to levels similar to those observed in E2-treated cells. Since E2 was shown to mediate its effects on some target genes through a cAMP- dependent pathway, we studied the interaction between E2 and agents that are known to increase intracellular cAMP. Forskolin (10-8 M) and dibutyryl cAMP (10-3 M) increased IGF-I mRNA levels sixfold, and cotreatment with E2 did not affect these changes, consistent with a possible mediation of the estrogen effect on IGF-I gene expression by cAMP. We conclude that in human osteoblastic cells, the IGF-I gene is a target for estrogen action, suggesting that IGF-I may mediate part of the effects of estrogen in human bone.
KW - Bone
KW - Estradiol
KW - Osteoblast
KW - PCR
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U2 - 10.1007/s002239900395
DO - 10.1007/s002239900395
M3 - Article
C2 - 9405735
AN - SCOPUS:0031985268
SN - 0171-967X
VL - 62
SP - 60
EP - 66
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 1
ER -