SERMs and SARMs: detection of their activities with yeast based bioassays

J Steroid Biochem Mol Biol. 2010 Jan;118(1-2):85-92. doi: 10.1016/j.jsbmb.2009.10.007. Epub 2009 Oct 31.

Abstract

Selective estrogen receptor modulators (SERMs) and selective androgen receptor modulators (SARMs) are compounds that activate their cognate receptor in particular target tissues without affecting other organs. Many of these compounds will find their use in therapeutic treatments. However, they also will have a high potential for misuse in veterinary practice and the sporting world. Here we demonstrate that yeast estrogen and androgen bioassays can be used to detect SERMs and SARMs, and are also useful screening tools to investigate their mode of action. Six steroidal 11beta-substituents of E2 (SERMs) and some arylpropionamide- and quinoline-based SARMs were tested. In addition, 7 compounds previously tested on AR agonism and determined as inactive in the yeast androgen bioassay, while QSAR modelling revealed strong binding to the human androgen receptor, are now shown to act as AR antagonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / analysis*
  • Androgen Receptor Antagonists*
  • Androgens* / analysis*
  • Animals
  • Biological Assay / methods*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Estradiol / analogs & derivatives
  • Estradiol / analysis
  • Estrogen Receptor alpha / agonists
  • Estrogen Receptor alpha / antagonists & inhibitors
  • Estrogen Receptor alpha / genetics
  • Green Fluorescent Proteins / genetics
  • Humans
  • Molecular Structure
  • Receptors, Androgen / genetics
  • Selective Estrogen Receptor Modulators / analysis*
  • Substance Abuse Detection / methods
  • Transcriptional Activation / genetics
  • Transfection
  • Yeasts / genetics
  • Yeasts / metabolism*

Substances

  • Androgen Antagonists
  • Androgen Receptor Antagonists
  • Androgens
  • Estrogen Receptor alpha
  • Receptors, Androgen
  • Selective Estrogen Receptor Modulators
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Estradiol