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Testosterone Reverses the Urethra Hypercontractility in Ovariectomized Rat: Role of Voltage‐Operated Calcium Channel
Author(s) -
Bonilla Sandra Milena,
Antunes Edson
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08980
Subject(s) - endocrinology , medicine , ovariectomized rat , urethra , testosterone (patch) , nifedipine , chemistry , l type calcium channel , overactive bladder , dihydrotestosterone , verapamil , androgen , calcium , calcium channel , urology , estrogen , hormone , alternative medicine , pathology
Introduction and Aim Postmenopausal women exhibit overactive bladder (OAB), as evidenced by urgency, frequency and noctúria (1). Ovariectomized (OVX) rats display OAB and urethral hypercontractility that is normalized by in vivo testosterone replacement (2). Androgen receptors (AR) have been found in urinary bladder, suggesting they play an important role in the urinary continence (3,4). However, the mechanism of action of testosterone in urethra of female rats has not been elucidated. L‐type voltage‐operated calcium channels (VOCC) are implicated in urinary contraction during the voiding phase (4). We hypothesized here that testosterone via VOCC activation regulates the female urethra. This study aimed therefore to evaluate the effects of testosterone and its modulation by VOCC on urethra contractility in OVX rats. Materials and methods Two‐month old female Sprague Dawley rats were submitted to bilateral ovariectomy, whereas Sham‐operated rat were manipulated but the ovaries were left intact. After 4‐month OVX, the urethra was removed, and concentration‐response curves to calcium chloride (CaCl 2 ; 10 μM – 300 mM) were performed in the presence of testosterone (100 nM; 30 min), vehicle (alcohol; 0.5 μL) and/or the VOCC inhibitor nifedipine (3 nM; 30 min). Results Bilateral OVX significantly increased the urethra contraction to compared with Sham group (P < 0.05). Testosterone (100 nM prevented CaCl 2 ‐induced urethral hypercontractility in OVX group. Pre‐incubation with nifedipine (3 nM) also reduced the contractile response to extracellular calcium in OVX group. In Sham group, testosterone and/or nifedipine had no effects. Conclusion Our data suggests that testosterone via non‐classical genomic pathway acts to inhibit VOCC to normalize the urethral hypercontractility in OVX rats. All animal procedures were approved by the Ethical Committee on Animals Use CEUA/UNICAMP (CEUA; No. 4421‐1, 5250‐1). Support or Funding Information FINANCIAL SUPPORT: FAPESP (2017/26564‐9).