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

The FASEB Journal 21aug03

Ivan Quesada, Esther Fuentes, M. Carmen Viso-León, Bernat Soria, Cristina Ripoll, and Angel Nadal
E-mail contact: nadal@umh.es

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 17b-E2 when acting through the classic estrogen receptors (ERs). Here, we show that the environmental estrogen Bisphenol-A and the native hormone 17b-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 17b-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 P-CREB 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.

Key words: xenoestrogens · estrogen receptors · islets of Langerhans · non-genomic