Tetrahydrogestrinone induces a genomic signature typical of a potent anabolic steroid.
Tetrahydrogestrinone (THG) is a recently identified compound having the greatest impact in the world of sports. In order to obtain a highly accurate and sensitive assessment of the potential anabolic/androgenic activity of THG, we have used microarrays to identify its effect on the expression of practically all the 30,000 genes in the mouse genome and compared it with the effect of dihydrotestosterone (DHT), the most potent natural androgen. Quite remarkably, we found that 671 of the genes modulated by THG in the mouse muscle levator ani are modulated in a similar fashion by DHT, while in the gastrocnemius muscle and prostate, 95 and 939 genes respectively, are modulated in common by the two steroids. On the other hand, THG is more potent than DHT in binding to the androgen receptor, while, under in vivo conditions, THG possesses 20% of the potency of DHT in stimulating prostate, seminal vesicle and levator ani muscle weight in the mouse. The present microarray data provide an extremely precise and unquestionable signature of the androgenic/anabolic activity of THG, an approach which should apply to the analysis of the activity of any anabolic steroid.
Labrie
Fernand
F
Molecular Endocrinology and Oncology Laboratory, Laval University Medical Research Center (CRCHUL) and Laval University, Québec City, G1V 4G2, Canada. fernand.labrie@crchul.ulaval.ca
Luu-The
Van
V
Calvo
Ezequiel
E
Martel
Céline
C
Cloutier
Julie
J
Gauthier
Sylvain
S
Belleau
Pascal
P
Morissette
Jean
J
Lévesque
Marie-Hélène
MH
Labrie
Claude
C
D045930:Anabolic Agents / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D013196:Dihydrotestosterone / Q000378:metabolism; D004300:Doping in Sports; D015870:Gene Expression; D020869:Gene Expression Profiling; D005867:Gestrinone / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D015741:Metribolone / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000378:metabolism; D011485:Protein Binding; D011897:Random Allocation; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000235:genetics / Q000378:metabolism
D045930:Anabolic Agents; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D005867:Gestrinone; D015741:Metribolone; D013739:Testosterone; C479553:tetrahydrogestrinone