1 – Effects of Dutasteride, Finasteride and CypAc on [14C]-Testo metabolism (A) and DHT production (B); 24h assay.
2 – (A) Effects of Dutasteride, Finasteride and CypAc on RASD1 expression after 4 h stimulation with DHT or Testo – (B) Effects of drugs (1µM) on AR translocation (1h assay with DHT) – Effects of drugs (1µM) on lipid accumulation (7days assay, with DHT or Testo).
CONCLUSIONS
In this model,
– Dutasteride is a strong inhibitor of DHT production (1000-fold more active than Finasteride).
– CypAc strongly inhibits the transcription of AR-dependent genes induced by DHT or Testo, without interfering with AR translocation (nuclear effects).
– CypAc is not as effective as expected on the functional lipid accumulation assay. Dutasteride is active in the lipid accumulation assay even in the presence of DHT as inducer, indicating potential additional targets than 5-α-reductase. Taken together it indicates that there is no direct correlation between early inhibitory processes and the final functional effects after 7 days.
– The androgen lipid accumulation assay is suitable for high throughput testing of various compounds with various mechanisms of action, including anti-androgens, cell metabolism inhibitors, etc. Among other, mTOR inhibitors are effective. In these experimental conditions, isotretinoin, which is a reference treatment for acne does not interfere with this androgen-stimulated lipid accumulation (even shows an opposite effect).
REFERENCES
1 Barrault et al. (2015) J Steroid Biochem Mol Biol ;152:34-44
2 Bernard et al. (2000) Int J Cosmet Sci ;22:397-407
Innate immunity activation of sebocyte cells by living bacteria. Evidence of a potential immunosuppressive effect of DHT.
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