[h=1]The direct inhibitory effect of dutasteride or finasteride on androgen receptoractivity is cell line specific.[/h]
[h=4]BACKGROUND:[/h]Finasteride and dutasteride were developed originally as 5α-reductase inhibitors to block the conversion of testosterone to dihydrotestosterone (DHT). These drugs may possess off-target effects on theandrogen receptor (AR) due to their structural similarity to DHT.
[h=4]METHODS:[/h]A total of four human prostate cancer cell models were examined: LNCaP (T877A mutant AR), 22Rv1 (H874Y mutant AR), LAPC4 (wild-type AR), and VCaP (wild-type AR). Cells were cultured in 10% charcoal-stripped fetal bovine serum, either with or without DHT added to the medium. AR activity was evaluated using the ARE-luciferase assay or the expression of AR regulated genes.
[h=4]RESULTS:[/h]Dutasteride was more potent than finasteride in interfering with DHT-stimulated AR signaling. Disruption of AR function was accompanied by decreased cell growth. Cells that rely on DHT for protection against death were particularly vulnerable to dutasteride. Different prostate cancer cell models exhibited different sensitivities todutasteride and finasteride. LNCaP was most sensitive, LAPC4 and VCaP were intermediate, while 22Rv1 was least sensitive. Regardless of the AR genotype, if AR was transfected into drug-sensitive cells, AR was inhibited by drug treatment; and if AR was transfected into drug-resistant cells, AR was not inhibited.
[h=4]CONCLUSIONS:[/h]The direct inhibitory effect of dutasteride or finasteride on AR signaling is cell line specific. Mutations in the ligand binding domain of AR do not appear to play a significant role in influencing the AR antagonistic effect of these drugs. Subcellular constituent is an important factor in determining the drug effect on AR function.
[h=1]Treatment of recurrent priapism in sickle cell anemia with finasteride: a new approach.[/h]
[h=4]OBJECTIVES:[/h]To determine whether the use of finasteride controls recurrent priapism in patients with sickle cell anemia.
[h=4]METHODS:[/h]Thirty-five patients with recurrent priapism because of sickle cell disease received finasteride during 120 days. The initial dose was decreased every 40 days, from 5 mg/d to 3 mg and then to 1 mg of finasteride until the end of 120 days. Five groups (G) were created based on priapism episodes in a month: G0, no episode; G1, 1-15 episodes; G2, 16-30; G3, 31-45; and G4, >45 episodes.
[h=4]RESULTS:[/h]Records on day 0: G0, no patient; G1, 7 (20%); G2, 21 (60%); G3, 4 (12%); and G4: 3 (8%). After 40 days of using 5 mg/d finasteride we found the following results: G0, 5 patients (14%); G1, 19 (55%); G2, 8 (23%); G3, 3 (8%); and G4, none. At the end of the 40-day period, using 3 mg/d finasteride, the findings were as follows: G0, 19 patients (55%); G1, 14 (39%); G2, 2 (6%); G3, none; and G4, none. The findings after 120 days with 1 mg/d finasteride for the last 40 days were as follows: 16 patients (46%) and G1, 16 (46%). In 1 patient, the dose was increased to 3 mg and in 2 patients, to 5 mg, so as to achieve remission.
[h=4]CONCLUSIONS:[/h]To our knowledge, this is the first study demonstrating that the use of finasteride could decrease and control the number of priapism recurrences in patients with sickle cell anemia, with fewer side effects than other drugs currently used.