Emerging Chemicals Targeting Aromatase: Protective Compounds or Endocrine Disruptors?

Abstract

Aromatase is the enzyme converting androgens into estrogens in the last step of steroid hormone synthesis. Being part of the endocrine system, it is one of the most important targets for compounds ranging from drugs developed since the 1980s for breast cancer treatment, to different kinds of xenobiotics from different sources such as food, pollution and cosmetics.

Different pathologies correlate with abnormal levels of estrogens produced by aromatase that is expressed also in different extragonadal sites as a single protein. Thus, a compound that inhibits aromatase activity can be protective towards pathologies that correlate with high levels of estrogens and dangerous for pathologies that correlate with low levels of these hormones.

We review the effect of known protective and dangerous compounds such as the endocrine disruptors on aromatase activity focusing on the so‐called emerging pollutants that are warning the world attention owing to their wide use and the potential to contaminate surface water.

Key Concepts

  • Aromatase is the enzyme converting androgens into estrogens and it is the product of a single gene in most species.
  • Estrogens unbalance is nowadays associated with different abnormal conditions and pathologies.
  • Aromatase is the target for drugs currently used mainly for breast cancer therapy.
  • Aromatase is the target for natural compounds that have been shown to have health benefits.
  • Some of the so‐called endocrine disrupting chemicals that produce adverse health effects target aromatase.
  • Some emerging pollutants behave as endocrine disrupting chemicals and were found to affect aromatase activity.

Keywords: aromatase; endocrine disruptors; estrogens; breast cancer; neuroprotection; emerging pollutants

Figure 1. Effects of estrogens on a target cell. Once synthesised, androgens and estrogens can reach a target cell where they diffuse trough the membrane. Estrogens can also be locally produced if aromatase is expressed. In the target cell, estrogens associate with their receptors (ER) that dimerise and bind the estrogen response elements (EREs) on DNA (deoxyribonucleic acid) promoting the transcription of target genes.
Figure 2. Aromatase conversion of androgens into estrogens. Aromatase protein is linked to the endoplasmic reticulum through a N‐terminal helix. The crystal structure and the molecular electrostatic potential surface of the protein are shown.
Figure 3. Chemical structure of the compounds present in the watch list published in the Directive EU 39/2013.
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Di Nardo, Giovanna, and Gilardi, Gianfranco(Feb 2018) Emerging Chemicals Targeting Aromatase: Protective Compounds or Endocrine Disruptors?. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0027581]