Androgen receptor mRNA measured by quantitative real time PCR is decreased in the urethral mucosa of patients with middle idiopathic hypospadias.

Androgen action is exerted through the androgen receptor. The normal 46,XY genital virilization depends on androgen receptor gene expression, which is tissue specific, and requires normal androgen receptor mRNA levels in androgen sensitive tissues. Hypospadias is a frequent male genital abnormality, potentially related to reduced androgen sensitivity in genital tissues. The aim of this study was to compare, by quantitative real time PCR, the amount of androgen receptor mRNA in cells obtained from the urethral mucosa of patients with middle idiopathic hypospadias with the androgen receptor mRNA levels observed in control phimosis subjects with eutopic urethral opening. Prepubertal individuals were studied, including 41 controls and 17 hypospadias patients with mean (SD) ages of 4.7 (2.1) years and 4.0 (3.0) years, respectively. We observed significantly less androgen receptor mRNA in the urethral mucosa of patients with hypospadias than in the controls (p=0.002). The correlation between the level of androgen receptor mRNA expression and the penile size was almost statistically significant only in hypospadias patients (r=0.47; p=0.053). We also established the number of CAG repeats in exon 1 of the androgen receptor gene by GeneScan analysis. No significant difference was observed in the number of CAG repeats when patients and controls were compared. A negative correlation between the CAG repeats and penile size was detected in patients with hypospadias, but not in controls. Our data suggest that a critical lower level of androgen receptor mRNA expression could be a determining factor in the development of middle hypospadias.

Gastrocystoplasty and chronic renal failure: an acid-base metabolism study.

PURPOSE: To verify in an experimental model whether gastrocystoplasty may protect patients with chronic renal failure from acid loading associated acidosis a wedge-shaped portion of the middle stomach was used to improve bladder capacity in animals with chronic renal failure. MATERIALS AND METHODS: An experimental model was used to study 112 adult female Wistar rats (EPM-1) weighing between 156 and 259 gm. The animals were randomly assigned to groups, including 41 controls, 24 undergoing five-sixths nephrectomy to create chronic renal failure, 26 undergoing gastrocystoplasty and 21 undergoing gastrocystoplasty and five-sixths nephrectomy to create renal failure. To provide an acid overload a 5% NH(4)Cl diet was administered to a subgroup of each group. Two months after surgery 24-hour urine was collected, and volume and pH were measured as well as the amount of bicarbonate, ammonium, titratable acidity and chloride. The animals were then exsanguinated through an abdominal aorta puncture. The blood was used for blood gas analysis and to measure sodium, potassium, chloride, ionized calcium and creatinine. RESULTS: When undergoing an acid overload, the animals with gastrocystoplasty had no acidosis since acid radicals were eliminating in the urine as NH(4)Cl. When given the same acid overload, metabolic acidosis developed in the animals with gastrocystoplasty and chronic renal failure. CONCLUSIONS: Gastrocystoplasty protected healthy rats from acidosis when they were given an acid overload but failed to protect the rats with chronic renal failure under the same conditions.