Vitamin D regulates human ectocervical epithelial cell proliferation and insulin-like growth factor-binding protein-3 level

The differentiation status of the cervical epithelial cell has an important influence on responsiveness to estrogens and progestins, Several agents, i ncluding glucocorticoids and retinoids, are known to influence cervical cel l differentiation. However, the effects of vitamin D have not been examined . Vitamin D is known to regulate cell proliferation and gene expression in a variety of epithelial cells. In the present study we investigated the abi lity of 1 alpha 25-dihydroxyvitamin D-3 (D3) to regulate cell proliferation and expression of insulin-like growth factor-binding protein-3 (IGFBP-3) i n human ectocervical epithelial cells. ECE16-1, a non-tumorigenic cervical cell line, was growth inhibited by D3 with maximal inhibition at 1000 nM. I GFBP-3 levels increased in parallel with the growth inhibition. IGFBP-3 lev els were half-maximally increased at approximately 10-100 nM and maximally increased (10- to 30-fold) at 1000 nM D3. These studies show that vitamin D regulates cervical epithelial cell gene regulation and cell proliferation and that IGFBP-3 may be an in vivo marker of vitamin D action in the cervix .