INVESTIGATIVE UROLOGY

Analysis of the modifications in the composition of bladder glycosaminoglycan and collagen as a consequence of changes in sex hormones associated with puberty or oophorectomy in female rats
Cabral CA, Sampaio FJ, Cardoso LE
Urogenital Research Unit, State University of Rio de Janeiro, Brazil
J Urol. 2003;170: 2512-6

• Purpose: The effects of female sex hormones on rat vesical extracellular matrix were evaluated by analyzing glycosaminoglycan (GAG) and collagen composition under different hormonal conditions.
• Materials and Methods: Bladders were obtained from Wistar rats, including young prepubertal females at age 30 days (YF), and adult intact females (AF), adult oophorectomized females (AOF), adult males and adult sham operated females at age 120 days. Oophorectomy and sham operation were performed at age 30 days. Bladders were analyzed for total GAG and collagen concentration per mg dry tissue and for the contents of GAG species, as determined by agarose electrophoresis and reported as the percent of total sulfated GAG.
• Results: Collagen concentration in AF (54.80 +/- 4.60 microg/mg) was different from that in YF (34.52 +/- 5.29 microg/mg, p <0.001) and AOF (63.25 +/- 3.51 microg/mg, p <0.001). GAG concentration in AF (0.71 +/- 0.18 microg/mg) was different from that in YF (0.45 +/- 0.07 microg/mg, p <0.001) and males (0.46 +/- 0.10 microg/mg, p <0.001). The GAG species detected were dermatan sulfate and heparan sulfate. Dermatan sulfate content in AF (90.9% +/- 2.8%) was different from that in YF (86.6% +/- 2.4%, p <0.005), AOF (87.9% +/- 2.1%, p <0.005) and males (87.7% +/- 4.7%, p <0.005). Heparan sulfate content in AF was 9.1% +/- 2.8%, which differed from that in YF (13.4% +/- 2.4%, p <0.025) and AOF (11.2% +/- 2.9%, p <0.025).
• Conclusions: Extracellular matrix of the female rat bladder undergoes marked remodeling during normal growth up to early adulthood with important consequences for vesical viscoelastic properties. Also, oophorectomy performed at a prepubertal age may lead to greater vesical wall stiffness.
  
  
• Editorial Comment
  Sex hormones have been shown to variously affect the synthesis of extracellular matrix (ECM) molecules by mesenchymal cells such as fibroblasts and smooth muscles cells, both in vivo and in vitro. This effect is exerted on several tissues and organs and has, in many cases, a normal regulatory role. The ECM may also undergo abnormal modifications, and these have been implicated with many diseases, including urinary tract disorders. In the present study, the effects of female sex hormones on the biochemical composition of vesical glycosaminoglycans (GAG) and collagen in rats under different hormonal conditions were evaluated.
  The results show that variations in the plasma levels of female sex hormones parallel different changes in the ECM composition of the rat bladder wall. During the normal growth of the female rat from a pre-pubertal age to early adulthood, there are marked increases in both total GAG and collagen concentrations, together with a small increase in dermatan sulfate and a more important decrease in heparan sulfate. Compared to the intact adult females, the bladders from oophorectomized adult females had a slightly higher collagen concentration but presented no change in total GAG, whereas the dermatan sulfate and heparan sulfate contents were decreased and increased, respectively, which may lead to greater vesical wall stiffness. Bladders from adult males differ from those of females of comparable age in that they have less total GAG, and hence a higher collagen: GAG ratio, and slightly less dermatan sulfate. In conclusion, this work demonstrates that the ECM of the female rat bladder undergoes a marked remodeling during normal growth up, which can lead to important consequences for vesical viscoelastic properties.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil