Low doses of the endocrine disruptor Bisphenol‐A and the native hormone 17β‐estradiol rapidly activate the transcription factor CREB

Resumen

ABSTRACT Endocrine‐disrupting chemicals (EDCs) are hormone‐like agents present in the environment that alter the endocrine system of wildlife and humans. Most EDCs have potencies far below those of the natural hormone 17β‐E2 when acting through the classic estrogen receptors (ERs). Here, we show that the environmental estrogen Bisphenol‐A and the native hormone 17β‐E2 activate the transcription factor, cAMP‐responsive element binding protein (CREB) with the same potency. Phosphorylated CREB (P‐CREB) was increased after only a 5‐minute application of either BPA or 17β‐E2 in a calcium‐dependent manner. The effect was reproduced by the membrane‐impermeable molecule E2 conjugated to horseradish peroxidase (E‐HRP). The increase in PCREB was not modified by the anti‐estrogen ICI 182,780. Therefore, low‐dose of BPA activates the transcription factor CREB via an alternative mechanism, involving a non‐classical membrane estrogen receptor. Because these effects are elicited at concentrations as low as 10 –9 M, this observation is of environmental and public health relevance.