Evaluation of MENT on primary cell cultures from benign prostatic hyperplasia and prostate carcinoma.
7-alpha-Methyl-19-Nortestosterone (MENT) is a synthetic androgen more potent than testosterone (T) and cannot be reduced at 5-alpha position. No important effects of MENT on prostate growth have been reported. However, little is known about the effect of MENT on benign prostatic hyperplasia (BPH) or prostate carcinoma (CaP). We evaluate the effect of MENT, T and dihydrotestosterone (DHT) on secretion, proliferation and gene expression of primary cell cultures from human BPH and CaP. Moreover, the effect of these androgens was examined in the presence of finasteride to determine the influence of the 5-alpha reductase (5-AR) activity on the androgenic potency. BPH and CaP primary cultures were treated with 0, 1, 10 and 100 nM of T, MENT or DHT during 24 and 48 h. Prostate-specific antigen (PSA) was measured by micro particles immunoassay and proliferation rate by spectrophotometric assay (MTT) and by the immunochemical detection of the proliferation marker Ki-67. Gene expression of FGF8b (androgen sensitive gene) was evaluated by semi-quantitative RT-PCR. Results showed that MENT treatments increased PSA secretion and proliferation rate with a potency ranged between T and DHT. Similar effects of MENT were observed in both BPH and CaP cultures. The studies with finasteride showed that in BPH and CaP cells, the conversion of T into DHT significantly contributes to its effect on the proliferation and PSA secretion, and corroborated the resistance of MENT to the 5-AR. The effect of MENT on the gene expression of FGF8b in CaP cells was similar to T and lower than DHT. It is concluded that MENT increases proliferative and secretory activities and gene expression on pathological prostate cells although in less extent than the active metabolite DHT. Furthermore, the fall of endogenous concentration of T during MENT treatment anticipates that this androgen will be of low impact for the prostate.
Mendoza
Patricia
P
Laboratory of Molecular and Cellular Andrology, Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Sánchez
Catherine
C
Contreras
Héctor R
HR
Vergara
Jorge
J
Acevedo
Cristian
C
Cabezas
Juan
J
Huidobro
Christian
C
Noé
Gabriela
G
Castellón
Enrique A
EA
D000728:Androgens / Q000378:metabolism / Q000627:therapeutic use; D013196:Dihydrotestosterone / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D018120:Finasteride / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D045165:Testosterone Congeners / Q000378:metabolism / Q000627:therapeutic use
D000728:Androgens; D045165:Testosterone Congeners; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride; D009277:Nandrolone; D017430:Prostate-Specific Antigen