The ontogenetic expression pattern of type 5 phosphodiesterase correlates with androgen receptor expression in rat corpora cavernosa.
BACKGROUND
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.


OBJECTIVE
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).


METHODS
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).


CONCLUSIONS
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
Eleonora
E
Course of Endocrinology and Medical Sexology, Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.
Rossi
Simona
S
Giansante
Nadia
N
Gravina
Giovanni Luca
GL
Castri
Alessandra
A
Dolci
Susanna
S
Botti
Flavia
F
Morelli
Annamaria
A
Di Luigi
Luigi
L
Pepe
Mario
M
Lenzi
Andrea
A
Jannini
Emmanuele A
EA
D000818:Animals; D015153:Blotting, Western; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006157:Guanosine Monophosphate / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D010413:Penis / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D018076:DNA, Complementary; D011944:Receptors, Androgen; D012313:RNA; D006157:Guanosine Monophosphate; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5