Testosterone positively regulates functional responses and nitric oxide expression in the isolated human corpus cavernosum

Gur S., Alzweri L., Yilmaz-Oral D., Kaya-Sezginer E., Abdel-Mageed A., Dick B., ...Daha Fazla

ANDROLOGY, cilt.8, sa.6, ss.1824-1833, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 8 Sayı: 6
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1111/andr.12866
  • Dergi Adı: ANDROLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1824-1833
  • Anahtar Kelimeler: hypogonadism, testosterone, human corpus cavernosum, phosphodiesterase type 5 enzyme, relaxation, DIRECT ANDROGEN REGULATION, ERECTILE FUNCTION, HYPOGONADAL MEN, CORONARY-ARTERIES, PHOSPHODIESTERASE TYPE-5, ENDOTHELIAL DYSFUNCTION, REPLACEMENT THERAPY, OXIDATIVE STRESS, PENILE ERECTION, NERVE-FIBERS
  • Çukurova Üniversitesi Adresli: Evet

Özet

Background Testosterone (T) deficiency is associated with erectile dysfunction (ED). The relaxant response of T on the corporal smooth muscle through a non-genomic pathway has been reported; however, the in vitro modulating effects of T on human corpus cavernosum (HCC) have not been studied. Objectives To compare the effects of various concentrations of T on nitric oxide (NO)-dependent and nitric oxide-independent relaxation in organ bath studies and elucidate its mode of action, specifically targeting the cavernous NO/cyclic guanosine monophosphate (cGMP) pathway. Materials and methods Human corpus cavernosum (HCC) samples were obtained from men undergoing penile prosthesis implantation (n = 9). After phenylephrine (Phe) precontraction, the effects of various relaxant drugs of HCC strips were performed using organ bath at low (150 ng/dL), eugonadal (400 ng/dL), and hypergonadal (600 ng/dL) T concentrations. The penile tissue measurements of endothelial nitric oxide synthase (eNOS), neuronal (n)NOS, and phosphodiesterase type 5 (PDE5) were evaluated via immunostaining, Western blot, cGMP and nitrite/nitrate (NOx) assays. Results Relaxation responses to ACh and EFS in isolated HCC strips were significantly increased at all T levels compared with untreated tissues. The sildenafil-induced relaxant response was significantly increased at both eugonadal and hypergonadal T levels. Normal and high levels of T are accompanied by increased eNOS, nNOS, cGMP, and NOx levels, along with reduced PDE5 protein expression. Conclusion This study reveals an important role of short-term and modulatory effects of different concentrations of T in HCC. T positively regulates functional activities, inhibition of PDE5 expression, and formation of cGMP and NOx in HCC. These results demonstrate that T indirectly contributes to HCC relaxation via downstream effects on nNOS, eNOS, and cGMP and by inhibiting PDE5. This action provides a rationale for normalizing T levels in hypogonadal men with ED, especially when PDE5 inhibitors are ineffective. T replacement therapy may improve erectile function by modulating endothelial function in hypogonadal men.