Download tetrahydrogestrinone (THG)

Endocrine pharmacological
tetrahydrogestrinone (THG)
1
characterization
1
of
the
“designer
drug”
2
Michna Horst , Selg Peter-Johannes , Nishino Tsuyuki
1
Institute of Public Health Research, Faculty of Sport Science, Technical University of Munich, Germany
2
Biological Sciences, Galvin Life Science Building, University of Notre-Dame, Indiana, USA
Introduction
Tetrahydrogestrinone (THG) recently showed great impact on sports and was the second so called “designer drug”
detected besides Desoxymethyltestosterone (DMT) and Norbolethone. The biochemical characterization of THG is
as follows: it is a “designer” steroid based on the steroids trenbolone and gestrinone. Both of these parent
compounds are only suitable to be administered by injection.
Synthesis
The synthesis of THG starts with
gestrinone and its nickel-catalyzed
hydrogenation
(17α-alkine)
resulting in THG. By modifying the
17α-position, THG becomes orally
active. THG is a very strong
anabolicum with an increased risk
of liver damage and the incidence
of general side effects usually
caused by steroids.
OH
OH
H
OH
H2, Ni
H
O
Trenbolone
O
O
Gestrinone
Tetrahydrogestrinone
OH
17α-postion
O
Fig. 1: Tetrahydrogestrinone (THG) is a very strong steroid with an
increased risk of liver damage
Endocrine profile
THG did neither display (Anti-)estrogenic nor (Anti-)glucocorticoid activity in our classical preclinical test systems.
THG did not inhibit androgen receptors activation by testosterone or progesterone receptors activation by
progesterone, nor did THG have endogen receptor agonist or antagonist activity (Death et al. 2004). Based on the
chemical structure of the compound special emphasize was given to elucidate the progestational and androgen like
activity. Whereas no anti-androgenic or anti-progestational activity was detected, the compound in fact induced both
biologically relevant androgen and progestational activity in all test systems: The progestational activity was
analysed in estradiol primed rabbits after a treatment period of five days (“Clauberg assay”) and in a bioassay to
measure the proliferative effects of progesterone on the growth of tubulo-alveolar buds (morphometric evaluation,
biochemical DNA, RNA analysis) in the mammary gland in ovariectomized and estrone substituted rats. The
androgenic effects of THG were analysed in the classical orchiectomized mouse and rat model after s. c. treatment
periods up to 12 days in direct comparison to testosterone propionate (o.1mg/animal/day s. c.): THG induced (a dose
dependent) androgenic effect on prostate and vesicular seminales parameters and LH serum levels in doses of
1,3,10mg/animal. This androgenic stimulation could be antagonized by the simoultaneous administration of the pure
antiandrogen Flutamide (3mg).
Conclusion
THG, like other anabolic steroids, exerts androgenic and progestational effects in the standard assays to predict
activity in humans. Therefore, this compound may induce strong biomedical side effects which have been already
reported for several substances prohibeted by the list (Peters et al. 2001). Accordingly, THG must be considered as a
very perilous drug, especially when used for doping purposes.
References
Death A K, et al. (2004). J Clin EndocrinolMetab 89: 2498–2500
Peters et al. (2001). Biomedical side effects of doping