Tetrahydrogestrinone is a potent but unselective binding steroid and affects glucocorticoid signalling in the liver

Toxicol Lett. 2006 Jun 20;164(1):16-23. doi: 10.1016/j.toxlet.2005.11.006. Epub 2005 Dec 13.


Tetrahydrogestrinone (THG) is a steroid recently identified to be misused as doping agent. However, the knowledge on functions of this substance in humans or animal models is rather limited. Therefore, it was our aim to further characterize the pharmacological profile of THG and identify potential adverse side effects. THG was synthesized, the purity was confirmed and its biological activity was tested. The potency of THG to transactivate AR dependent reporter gene expression was two orders of magnitude lower compared to dihydrotestosterone. THG binds with high affinity but unselective to the androgen (AR), progesterone (PR), glucocorticoid (GR) and mineralocorticoid (MR) receptor. Treatment of orchiectomised rats with THG resulted in a stimulation of prostate, seminal vesicle and levator ani muscle, indicating androgenic and anabolic properties. In the liver THG, in contrast to testosteronepropionate (TP), down regulates the expression of the GR dependent tyrosine aminotransferase gene (TAT). In summary, our results demonstrate that THG is not a specific AR agonist. THG exhibits a high binding affinity to all tested steroid hormone receptors and binds with highest affinity to the GR. Our in vivo data are indicative of an anabolic and androgenic potency of THG, but the repression of TAT demonstrates that THG also interferes with the glucocorticoid hormone system. Therefore, it is conceivable that an intake will result in adverse side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anabolic Agents / adverse effects
  • Anabolic Agents / chemistry
  • Anabolic Agents / pharmacology*
  • Animals
  • Binding, Competitive
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Gestrinone / adverse effects
  • Gestrinone / analogs & derivatives*
  • Gestrinone / chemistry
  • Gestrinone / pharmacology
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Molecular Structure
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / pathology
  • Orchiectomy
  • Organ Size / drug effects
  • Prostate / drug effects
  • Prostate / pathology
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Receptors, Glucocorticoid / metabolism*
  • Seminal Vesicles / drug effects
  • Seminal Vesicles / pathology
  • Signal Transduction / drug effects*
  • Yeasts / genetics


  • Anabolic Agents
  • Receptors, Androgen
  • Receptors, Glucocorticoid
  • Gestrinone
  • tetrahydrogestrinone