Journal Article

Zinc Enhancement of 17β-Estradiol's Anabolic Effect in Osteoblastic MC3T3-E1 Cells

Matsui, T., Yamaguchi, M.

1997

Overview

The anabolic effect of 17β-estradiol in osteoblastic MC3T3-E1 cells was investigated. The cells were cultured for 3 days in the medium containing either vehicle or 17β-estradiol (10 -10 M). 17β-Estradiol significantly increased alkaline phosphatase activity and protein concentration in the cells. The steroid (10 M) also significantly elevated the cell numbers and the cellular DNA content. The anabolic effect by 17β-estradiol was blocked by the presence of dipicolinate (10 M), a chelator of zinc ion, suggesting a role of cellular zinc in osteoblastic cell function. The presence of zinc sulfate (10 M) or β-alanyl-L-histidinato zinc (AHZ) (10 M) significantly enhanced the 17β-estradiol (10 or 10 M)-induced increase of alkaline phosphatase activity and protein concentration in the cells; the effect of AHZ was greater than that of zinc sulfate. The enhancement by zinc compounds was not based on the augmentation of osteoblastic cell numbers. The co-addition of cycloheximide (10 M), an inhibitor of protein synthesis, completely blocked the zinc compound (10 M)-induced enhancement of 17β-estradiol's (10 M) effect to increase alkaline phosphatase activity and protein concentration in the cells. Moreover, the anabolic effect of 17β-estradiol together with or without zinc compounds was abolished by the presence of staurosporine (10 M), an inhibitor of protein kinase C, or of okadaic acid (10 M), an inhibitor of protein phosphatase. The present study demonstrates that the anabolic effect of 17β-estradiol is enhanced by zinc-chelating dipeptide in osteoblastic MC3T3-E1 cells, and that the enhancing effect may involve protein synthesis and protein kinase activity.