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

Autor: Gur S; Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA.; Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey., Alzweri L; Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA.; Division of Urology, Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA., Yilmaz-Oral D; Department of Pharmacology, Faculty of Pharmacy, Cukurova University, Adana, Turkey., Kaya-Sezginer E; Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey., Abdel-Mageed AB; Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA., Dick B; Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA., Sikka SC; Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA., Volkan Oztekin C; Department of Urology, Faculty of Medicine, University of Kyrenia, Turkish Republic of North Cyprus, Girne, Mersin 10, Turkey., Hellstrom WJG; Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA.
Jazyk: angličtina
Zdroj: Andrology [Andrology] 2020 Nov; Vol. 8 (6), pp. 1824-1833. Date of Electronic Publication: 2020 Aug 24.
DOI: 10.1111/andr.12866
Abstrakt: 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.
(© 2020 American Society of Andrology and European Academy of Andrology.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje