Low doses of the endocrine disruptor bisphenol-A and the native hormone 17beta-estradiol rapidly activate transcription factor CREB.
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 17beta-E2 when acting through the classic estrogen receptors (ERs). Here, we show that the environmental estrogen Bisphenol-A and the native hormone 17beta-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 17beta-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.
Institute of Bioengineering, Miguel Hernández University, Campus of San Juan, Alicante 03550, Spain.
Ivan
I
Quesada
Esther
E
Fuentes
M Carmen
MC
Viso-León
Bernat
B
Soria
Cristina
C
Ripoll
Angel
A
Nadal
D000818:Animals; D001559:Benzhydryl Compounds; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D002118:Calcium; D017362:Cyclic AMP Response Element-Binding Protein; D004958:Estradiol; D005947:Glucose; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds