BIPHASIC ESTROGEN RESPONSE ON BOVINE ADRENAL-MEDULLA CAPILLARY ENDOTHELIAL-CELL ADHESION, PROLIFERATION AND TUBE FORMATION

Abnormal angiogenesis underlies many pathological conditions and is cr itical for the growth and maintenance of various types of tumors, incl uding hormone-dependent cancers. Since estrogens are potent carcinogen s in humans and rodents, and are involved in regulating angiogenesis, this study: was designed to examine the effect of estrogen on the beha vior of an established bovine capillary endothelial cell line, a simpl e and physiologically relevant model of the capillary wall. The result s demonstrate that 17 beta-estradiol (E2), at different conditions, ex erts both stimulatory and inhibitory effects on endothelial cell adhes ion, proliferation and tube formation in vitro. Utilizing a cellular a ttachment assay, chronic exposure to nanomolar concentrations of E2 (i .e. 1 and 10 nM) increased endothelial cell adhesion significantly com pared to vehicle treated controls. Cellular adhesion was inhibited by micromolar concentrations of E2. Cell count, PCNA immunohistochemistry and Western blot analysis demonstrated enhanced cell proliferation at low E2 concentration in estrogen-deplete medium. Inhibition of cellul ar proliferation was observed in both estrogen-replete and deplete med ium at higher E2 concentrations (i.e. 1 and 10 mu M). Furthermore, in vitro tube formation increased up to 3.0 fold in the presence of 10 nM and higher E2 concentrations. The present observations indicate that in vitro regulation of capillary endothelial cell adhesion, proliferat ion and capillary tube formation by estrogen, are dose dependent.