Understanding the diversity of sex steroid action
- Department of Physiology, Institution of Biomedicine and Turku Center for Disease Modelling, University of Turku, Turku FI-20014, Finland
- (Correspondence should be addressed to M Poutanen; Email: matti.poutanen{at}utu.fi)
Steroidal estrogens are lipid-soluble compounds that are able to pass through the plasma membrane of cells by diffusion. According to the current knowledge, the three main naturally occurring estrogens are estrone (E1), estradiol (E2), and estriol. E2 is the most active estrogen and the predominant female sex steroid during the reproductive years. In addition to these classical estrogens, there are various other steroidal and non-steroidal compounds that are able to interact with estrogen receptors (ERs), and thus at least partially act as estrogens. These include novel endogenous ligands (Saijo et al. 2011), pharmacological (McDonnell & Wardell 2010) and dietary compounds (Müller et al. 2004), as well as synthetic agents, such as pesticides and plasticizers (Craig et al. 2011).
Two nuclear ER subtypes have been well characterized, namely ESR1 (ERα) and ESR2 (ERβ). The nuclear ERs act as transcription factors, activated by ligand binding, and resulting in the recruitment of various receptor-interacting proteins and transcription factors of the general transcription machinery (Bulynko & O'Malley 2011, Hedengran Faulds et al. 2012). Several splice variants of both ERs have been found in normal and cancerous tissue, but their specific …