Peripheral regulatory mechanisms in erection.
The most important pathway underlying the penile erection is the nonadrenergic/noncholinergic signalling, which through the release of nitric oxide (NO), leads to an intracellular increase of cyclic GMP (cGMP), the main secondary messenger mediating tumescence in the penis. Interestingly, both cGMP formation and degradation are affected by testosterone (T). In fact, beyond the well-known role of T in regulating sexual desire and NO release, recent experimental evidences from our group showed that T also regulates the expression of phosphodiesterase type 5 (PDE5), the hydrolytic enzyme involved in cGMP breakdown. This antithetic role of T seems to be the main way through which the peripheral hormonal regulation of penile erections occurs, allowing an important synchronization between erectile processes and sexual desire. Hence, erections are still possible in hypogonadal conditions where a decreased cGMP formation, because of impaired NO production, is counterbalanced by a reduced cGMP hydrolysis. The purpose of this review is to describe evidences about the peripheral role of T in regulating penile erection and to justify the importance to test T plasma levels in those patients with erectile dysfunction who do not respond to PDE5 inhibitors.
Morelli
A
A
Andrology Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy.
Filippi
S
S
Zhang
X-H
XH
Luconi
M
M
Vignozzi
L
L
Mancina
R
R
Maggi
M
M
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D006801:Humans; D007006:Hypogonadism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010410:Penile Erection; D010726:Phosphodiesterase Inhibitors / Q000145:classification / Q000378:metabolism*; D013739:Testosterone / Q000097:blood / Q000378:metabolism*
D010726:Phosphodiesterase Inhibitors; D009569:Nitric Oxide; D013739:Testosterone; D006152:Cyclic GMP