Endocrine Abstracts

Introduction: In humans, prostate PDE5 expression was prominently localized in the endothelial and smooth muscle cells of the vascular bed, suggesting a possible action of PDE5 inhibitors on prostate blood flow.Aim: To investigate PDE5 expression in human and rat lower urinary tract (LUT) tissues and determine the effects of PDE5 inhibition with tadalafil on prostatic blood perfusion.Main outcome measures: Human vesicular-deferenti...

One of the proposed mechanisms responsible for Diabetes mellitus (DM)-associated erectile (ED) dysfunction is overactivity of RhoA/ROCK signalling. Because statins may decrease RhoA activation, we investigated whether atorvastatin ameliorated DM-induced ED in alloxan-treated (100 mg/kg) rabbits (in vitro studies) and streptozotocin-treated (STZ, 50 mg/kg) rats (in vivo studies). A subgroup of diabetic animals received atorvastatin 5 mg/kg per daily 2 weeks before...

A previous study demonstrate that chronic tadalafil administration (2 mg/kg per day) was able to prevent some, but not all, penile alterations induced by long-term (3 months) bilateral cavernous neurotomy (BCN) in the rat. In particular, in vitro acetylcholine responsiveness and reduced eNOS and nNOS expression were not preserved, while PDE5 down-regulation, along with muscle/fiber ratio and hypoxygenation (hypoxyprobe) were significantly restored by chronic tadalafil (...

Epididymis (epi) is a sex steroid-sensitive duct provided with spontaneous motility, allowing sperm transport. We previously demonstrated that human epi expresses a high abundance of mRNA for ER-alpha and ER-beta. We demonstrated that in epi estrogens up-regulate either oxytocin (OT) responsiveness, acting at the receptor level, and responsiveness to endothelin-1 (ET-1), another well-known stimulator of epididymal motility. However, we did not find any significant change eithe...

BXL-628 is a non-hypercalcemic calcitriol analog successfully tested in a phase IIa trial for benign prostate hyperplasia therapy. Because part of low urinary tract symptoms (LUTS) are generated by overactive bladder (OAB) and bladder expresses the calcitriol receptor (VDR), we investigated the BXL-628 effects on bladder contractility and RhoA/ROK signalling activated in OAB, by in vivo (2-weeks; 30 mcg/Kg, Sprague-Dawley, SD, and spontaneously hypertensive rats, SHR) a...

Human bladder contraction mainly depends on Ca2+ influx, via L-type voltage-gated Ca2+ channels, and on RhoA/Rho-kinase contractile signalling, a pathway up-regulated in overactive bladder (OAB) syndrome. Elocalcitol (Elo) is a vitamin D receptor agonist inhibiting RhoA/Rho-kinase signalling in rat and human bladder, shown to ameliorate OAB symptoms in a clinical study. Since in normal bladder from Sprague–Dawley (SD) rats Elo treatment delayed the c...

The molecular mechanisms underlying the reawakening of hypothalamic GnRH neurons at puberty remain to be elucidated. Recently, the G protein-coupled receptor 54 (GPR54) and its endogenous ligand kisspeptin, encoded by the KISS1 gene, have been involved. In fact, GPR54 mutations cause idiopathic hypogonadotropic hypogonadism in human and mice. We used the previously characterized primary culture of human fetal olfactory GnRH-secreting neurons, FNC-B4, to study in vitro t...

The contractile RhoA/Rho-kinase (Rock) signalling pathway is up-regulated in penile tissue in animal models of experimental diabetes and has been proposed to contribute to diabetes-related erectile dysfunction (ED). In previous studies we demonstrated that testosterone (T) restores diabetes-induced ED by influencing the NO/cGMP/PDE5 pathway.AimTo investigate the effect of T on the RhoA/Rock signalling in course of diabetes.MethodsWe used two distinct animal models of chemical ...

Benign prostate hyperplasia (BPH) is the most common disease in the aging male, often comorbid with erectile dysfunction (ED). PDE5 inhibitors (PDE5i, sildenafil, tadalafil and vardenafil) decrease lower urinary tract symptoms (LUTS) in patients with ED and BPH. We studied PDE5 expression and activity in the human bladder and PDE5i effects both in vitro (human and rat) and in vivo (rat). PDE5 is highly expressed in rat and human bladder and immunolocalized in vas...