Protective Effect of 3, 3-Diindolylmethane on Bisphenol A Activated GPR30, RAS, PI3K/Akt Estrogenic Signaling Pathway in Female Sprague-Dawley Rats

Abstract

The present study was aimed to evaluate the protective effect of 3, 3-diindolylmethane (DIM) on bisphenol A (BPA) induced estrogen signaling in the mammary glands of female Sprague-Dawley rats. Chronic administration of BPA (10 μg/kg/bw) to rats exerts rapid estrogenic action via GPR30 and activate cascade of signaling molecule which induce cell proliferation in the mammary gland. Western blot analysis of mammary tissues shows over expression of GPR30, SRC, RAS, PI3K and Akt proteins and immunohistochemical analysis reveals over expression of PCNA and no significant changes in ERs. Further, oral administration of DIM (5 mg/kg/bw), alternative days to BPA treated rats for the period of 12 weeks show significant decrease in the expression pattern of GPR30, SRC, RAS, PI3K, Akt and PCNA. The results of our study demonstrate that BPA induces rapid action via the over expression of proteins in non-genomic estrogen signaling pathway. Administration of DIM inhibits the action of BPA by modulating the expression of proteins involved in GPR30 cascade signaling pathway mediated cell proliferation in mammary glands of female rats.