4-Hexylresorcinol exhibits different characteristics to estrogen

4-Hexylresorcinol (4HR) has been used as a food additive and antiseptic. The aim of this study was to evaluate whether the application of 4HR in breast cancer cells and ovariectomized rats showed estrogen-like effects. MCF-7 and SK-BR-3 cells were treated by solvent, 1-100 μMbisphenol-A (BPA), or 1-100 μM 4HR, respectively. 3-(4, 5-Dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blot for extracellular signal-regulated kinase-1/-2 (ERK1/2), phosphorylated ERK1/2 (p-ERK1/2), estrogen receptor-α (ERα), and ERβ were done. As an in vivo study, ovariectomized rats (n = 15) received solvent, 125 mg/kg of 4HR, or 10 μg of 17-β estradiol via daily subcutaneous injection for 7 days. Blood samples were obtained for evaluation of prolactin levels. Pituitary glands and uteruses were biopsied for histological evaluation and Western blot analysis. Compared with the control group, the application of 4HR decreased the proliferation of MCF-7 and SK-BR-3 cells, while the application of BPA increased (p < 0.05). The application of BPA increased the expression of ERα, ERβ, and p-ERK1/2, but 4HR did not change the expression of ERα, ERβ, or p-ERK1/2 in MCF-7 cells. In an animal model, the 4HR group showed similar levels of ERα, ERβ, and prolactin expression in the pituitary gland compared to the solvent only group, while the estradiol group showed higher levels. Serum prolactin levels were similar between the 4HR and solvent only groups. Taken together, 1-100 μM 4HR did not show BPA-like behavior in MCF-7 cells, and 125 mg/kg of 4HR daily subcutaneous injection for 7 days did not demonstrate estradiol-like effects in ovariectomized rats. Collectively, 4HR has no estrogen-like effects on both ERα-positive cells and estrogen-deficient rat models.