(247) A Rat Model for Bipolar Androgen Therapy is Evaluated for Its Effects on Erectile Dysfunction after Castration
S Gur, D Yilmaz-Oral, CV Oztekin, S Tetik-Rama, D Turkcan- Urology
- Reproductive Medicine
- Endocrinology
- Endocrinology, Diabetes and Metabolism
- Psychiatry and Mental health
Abstract
Introduction
Prostate cancer (PCa), an androgen-dependent tumor and one of the most prevalent cancers in males, has traditionally been treated with androgen suppression. In recent years, bipolar androgen treatment (BAT) has emerged as a potential therapeutic approach for men with metastatic castrate-resistant PCa. The control of testosterone (T) between castration and supraphysiological levels inhibits the proliferation of cancer cells and slows the progression of cancer. Furthermore, while there has been prior research between T and erectile function, there is no evidence linking BAT and erectile dysfunction (ED).
Objective
The purpose of the current investigation was to determine if BAT therapy was effective in treating ED in a castration-prone rat model.
Methods
Sprague-Dawley rats (n=30) were randomly divided into four groups: 1) Control, 2) Control rats-received BAT treatment, 3) castrated Rats, and 4) castrated rats-received BAT treatment. The rats were castrated by making bilateral scrotal incisions. A subcutaneous injection of testosterone propionate (250 mg/kg/week, intramuscular) was administered four weeks following castration. Four weeks after the initial dose, the second dose of the medication was given in the same manner. By stimulating the cavernous nerve, the intracavernosal pressure (ICP) to mean arterial pressure (MAP) ratio and total ICP were determined. Corpus cavernosum (CC) strips were used as in vitro preparations for evaluating the relaxant and contractile responses. Nitric oxide synthase (nNOS) and endothelial NOS (eNOS) protein expression was analyzed using Western blotting. Using Masson trichrome staining, the location of the smooth muscle in relation to the collagen was identified.
Results
Castrated rats' prostate weight was reduced when compared to uncastrated rats (P< 0.001). Compared to controls and castrated rats, BAT marginally boosted prostate weight reduction. The ICP/MAP ratio and total ICP for 7.5 V were lowest in castrated rats (P< 0.001 vs. controls). BAT enhanced ICP/MAP and total ICP responses (P<0.01 vs. castrated rats). In vitro, endothelium-dependent acetylcholine-induced relaxation at 1 nM (P 0.05 vs controls), endothelium-independent sodium nitroprusside-induced relaxation at 1 nM (P 0.01 vs controls), electrical field stimulation-induced relaxant response at 20 Hz (P<0.05 vs. controls) and sildenafil-induced relaxation at 10 M (P 0.05 vs controls) were all reduced in the CC strips from the castrated group. Additionally, the castrated group showed increased neurogenic contractile response at 40 Hz and the contractile response to phenylephrine at 1 mM (P 0.001 vs. controls). The variations in the relaxation and contractile responses were returned by BAT. The smooth muscle cell-to-collagen ratio and nNOS and eNOS protein expression were both markedly reduced in castrated rats, though BAT reversed these modifications.
Conclusions
The results of the study show that BAT improves neurogenic relaxation, endothelium relaxation, sildenafil-induced relaxing of the CC, and changes in penile morphology after castration. BAT might be a cutting-edge therapeutic approach for patients with castration-resistant prostate cancer who have an ED route.
Disclosure
No.