TY - JOUR
T1 - Modulation of response to estrogens in cultured human female bone cells by a non-calcemic Vitamin D analog
T2 - Changes in nuclear and membranal binding
AU - Somjen, Dalia
AU - Katzburg, Sara
AU - Sharon, Orly
AU - Kaye, Alvin M.
AU - Gayer, Batya
AU - Kohen, Fortune
AU - Hendel, David
AU - Posner, Gary H.
PY - 2004/5
Y1 - 2004/5
N2 - Estradiol17β (E2) and the phytoestrogens genistein (G), and daidzein (D) increase creatine kinase (CK) specific activity in primary cell cultures of human female to a greater extent in cells from pre-menopausal than post-menopausal women. Pretreatment with the non-calcemic analog of Vitamin D, JK 1624 F2-2 (JKF), upregulated this estrogenic response at all ages. In contrast, biochainin A (BA) and quercertin (Qu) increased CK with no age dependence or modulation by JKF pretreatment. Both ERα and ERβ present in the cells were upregulated by pretreatment with JKF, as measured by Western blot analysis. Real time PCR showed no significant change in ERα mRNA but a marked decrease in ERβ mRNA in both age groups after JKF treatment. Cells from both age groups had surface binding sites for E 2, shown by assays using cell impermeable Europium labeled ovalbumin-E2 conjugate (Eu-Ov-E2). Binding of [ 3H]-E2 to intracellular E2 receptors (ERs) was similar in both age groups with differences in phytoestrogenic competition. JKF pretreatment increased nuclear but decreased membranal binding in both age groups. These results provide evidence for membranal, in addition to nuclear estrogen receptors which are differentially modulated by a Vitamin D analog.
AB - Estradiol17β (E2) and the phytoestrogens genistein (G), and daidzein (D) increase creatine kinase (CK) specific activity in primary cell cultures of human female to a greater extent in cells from pre-menopausal than post-menopausal women. Pretreatment with the non-calcemic analog of Vitamin D, JK 1624 F2-2 (JKF), upregulated this estrogenic response at all ages. In contrast, biochainin A (BA) and quercertin (Qu) increased CK with no age dependence or modulation by JKF pretreatment. Both ERα and ERβ present in the cells were upregulated by pretreatment with JKF, as measured by Western blot analysis. Real time PCR showed no significant change in ERα mRNA but a marked decrease in ERβ mRNA in both age groups after JKF treatment. Cells from both age groups had surface binding sites for E 2, shown by assays using cell impermeable Europium labeled ovalbumin-E2 conjugate (Eu-Ov-E2). Binding of [ 3H]-E2 to intracellular E2 receptors (ERs) was similar in both age groups with differences in phytoestrogenic competition. JKF pretreatment increased nuclear but decreased membranal binding in both age groups. These results provide evidence for membranal, in addition to nuclear estrogen receptors which are differentially modulated by a Vitamin D analog.
KW - "Non-hypercalcemic" Vitamin D analogs
KW - Estrogen receptors α and β
KW - Membranal binding
KW - Phytoestrogens
UR - http://www.scopus.com/inward/record.url?scp=3042647169&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2004.03.005
DO - 10.1016/j.jsbmb.2004.03.005
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C2 - 15225807
AN - SCOPUS:3042647169
SN - 0960-0760
VL - 89-90
SP - 393
EP - 395
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
ER -