OBJECTIVE: To address the role of the androgen receptor (AR) on mRNA and protein levels in prepuces of boys with and without hypospadias.
PATIENTS AND METHODS: Data from 40 foreskin specimens of consecutive circumcised boys (20 with vs 20 without hypospadias) were enrolled in this prospective study. After surgery, samples were fixed in formaldehyde and frozen in liquid nitrogen. Total RNA was isolated from frozen tissue and transcribed to complementary DNA. The amount of AR mRNA was measured by quantitative real-time polymerase chain reaction and Western Blot and standardised, automated immunohistochemistry were used to assess AR protein levels.
RESULTS: The mean age at time of surgery was 61.8 and 30.9 months in boys without and with hypospadias, respectively. There was penile, coronal and sine hypospadias in seven (35%), nine (45%), and four (20%) boys, respectively. AR mRNA was significantly elevated in the prepuces of boys with hypospadias compared with boys without hypospadias, at a mean (sd) of 28.33 (5.39) vs 15.31 (1.85) (P = 0.013). Furthermore, the amount of AR protein was higher in boys with, compared with boys without hypospadias, at a mean (sd) of 133.25 (6.17) vs 100 (4.45) (P = 0.014).
CONCLUSIONS: Different AR mRNA expression and protein levels seem to be an indication of an AR signalling defect as a cause in boys with hypospadias. Decreased AR DNA binding and functional capability may result in a compensatory up-regulation of both AR mRNA and protein. Further studies are necessary to perform structural analysis of the AR and to corroborate these preliminary findings.
Written by:
Pichler R, Djedovic G, Klocker H, Heidegger I, Strasak A, Loidl W, Bektic J, Skradski V, Horninger W, Oswald J. Are you the author?
Department of Urology and Pediatric Urology, Medical University of Innsbruck, Linz, Austria.
Reference: BJU Int. 2013 Jul;112(2):265-70.
doi: 10.1111/j.1464-410X.2012.11731.x
PubMed Abstract
PMID: 23469946
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