Dutasteride-mediated morphological changes in the genitourinary tract associated with altered expression patterns of the androgen and estrogen receptors in male rats.
We evaluated the effects of dutasteride on the genitourinary tract using fifteen 8-week-old male Sprague-Dawley rats. Animals were divided into three groups comprising five animals each and treated as follows. Group A was a control group, members of Group B received oral administration of dutasteride 0.1 mg/kg/day from the age of 8 to 16 weeks, and members of Group C were castrated at the age of 8 weeks. All rats were killed at the age of 16 weeks for the sample collection of blood, bladder, prostate, seminal vesicles, and penis. Then, we evaluated the pathological examination for evaluating the tissue fibrosis and hormonal receptor expression. The results showed that the mean size of the prostate and seminal vesicles was smaller in Group B and Group C than in Group A. Serum and tissue concentrations of both testosterone and dihydrotestosterone were remarkably reduced in serum and all tissues in Group C compared with Group A. On the other hand, in Group B, only dihydrotestosterone was reduced in serum and penis. Histopathological examination revealed that Group C showed statistically significant histological changes, such as an increase in fibrotic tissue in the bladder, prostate, and penis. Similarly, Group B showed fibrotic changes in the prostate and penis compared with the Group A. Immunofluorescent staining revealed that the androgen receptor was more strongly expressed than the estrogen receptor beta in Group A. On the other hand, in Group C, weak expression of the androgen receptor and strong expression of the estrogen receptor beta was noted. In Group B, these changes were noted in the prostate and penis. These findings suggest that dutasteride cause morphological changes not only in prostate but also in penis. These changes are associated with altered expression patterns of androgen receptor and estrogen receptor.
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
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0000-0002-9375-5191
N
Enatsu
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
K
K
Chiba
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
K
K
Sumii
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
T
T
Fukuda
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
K
K
Okada
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
K
K
Matsushita
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
M
M
Fujisawa
D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology*; D000818:Animals; D013196:Dihydrotestosterone; D000068538:Dutasteride / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D010413:Penis / Q000187:drug effects / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D012669:Seminal Vesicles / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D013739:Testosterone; D000068538:Dutasteride
androgen receptor; dutasteride; estrogen receptor; penile fibrosis