The Ontogenetic Expression Pattern of Type 5 Phosphodiesterase Correlates with Androgen Receptor Expression in Rat Corpora Cavernosa

ABSTRACT Introduction The mechanisms controlling erection in animals and in humans are mainly age-dependent. However, the ontogenesis of the biochemical machinery of erection is largely unknown. Aim The aim of this article was to study the expression pattern of androgen receptor (AR) and the major cyclic guanosine monophosphate-hydrolyzing enzyme present in the corpora cavernosa, type 5 phosphodiesterase (PDE5), in the rat penis during development. Methods AR and PDE5 expression was tested on ribonucleic acids (RNAs) and proteins extracted from the whole penis or from primary cultures of smooth muscle cells obtained from the corpora cavernosa of 3- (rCC3), 20- (rCC20), and 60- (rCC60) day-old rats. Rat corpus cavernosum cells were characterized by immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Main Outcome Measures Expression of PDE5 and AR messenger RNA (mRNA) and protein have been measured by RT-PCR and Western blot, respectively. Results A significant increase in PDE5 mRNA expression was observed with RT-PCR from prepuberty to adulthood (0.5 ± 0.06 vs. 1.6 ± 0.046 arbitrary units [a.u.] P = 0.049). This age-dependent increase was mirrored by the increase in PDE5 protein expression found when comparing neonatal to adult corpus cavernosum smooth muscle cells (1.5 ± 0.26 vs. 4.9 ± 0.59 a.u. P = 0.0038) and the further 1.6-fold increase from rCC20 to rCC60 (4.9 ± 0.59 vs. 8.0 ± 0.8 a.u. P = 0.0024). This is the first demonstration of the ontogenetic profile of PDE5 expression in corpus cavernosum smooth muscle. As it has been demonstrated that androgens control PDE5 expression and that PDE5 inhibitors need an optimal androgenic milieu to act perfectly on erection, the expression of AR protein in rat corpus cavernosum cells was then tested by Western blot. A 7.0-fold increase was observed in primary cultured cells from 3 to 60 days old (1.4 ± 0.38 vs. 9.8 ± 1.3 a.u. P = 0.0052). Conclusion The increase in ARs during rat penile development parallels that of PDE5 RNA and protein, thus suggesting a positive effect of androgens on PDE5 expression. Carosa E, Rossi S, Giansante N, Gravina GL, Castri A, Dolci S, Botti F, Morelli A, Di Luigi L, Pepe M, Lenzi A, and Jannini EA. The ontogenetic expression pattern of type 5 phosphodiesterase correlates with androgen receptor expression in rat corpora cavernosa. J Sex Med 2009;6:388–396.