Objectives: To evaluate the mechanisms of growth hormone (GH) action on isolated human penile erectile tissue. Human GH (hGH) has been suggested to play a role in male reproductive function, including penile erection. Nevertheless, it still remains unclear which intracellular pathways mediate the physiological effects of GH on the human corpus cavernosum (HCC).
Methods: Using the organ bath technique, the effects of GH were investigated on electrical field stimulation (EFS)-induced relaxation of isolated HCC in the absence and presence of the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine (l-NOARG, 10 microm). Effects of GH on the production of tissue cyclic guanosine monophosphate (cGMP) in the absence and presence of ODQ and l-NOARG were also elucidated using radioimmunoassay.
Results: ODQ and l-NOARG abolished the relaxation of the tissue induced by EFS, whereas amplitudes were increased by physiological concentrations of GH (1-100 nm). The attenuation of EFS-induced amplitudes by l-NOARG but not ODQ was, in part, reversed by GH. The production of cGMP (pmol cGMP/mg protein) induced by 10 nm GH was abolished in the presence of 10 microm ODQ. In contrast, the combination of GH (10 nm) and l-NOARG (10 microm) maintained cGMP production significantly greater than baseline (0.68 +/- 0.36 vs 1.07 +/- 0.48 pmol cGMP/mg protein).
Conclusions: Our data provide evidence that GH may act on human HCC by an NO-independent effect on guanylyl cyclase activity and may thus explain how growth factors, such as hGH, regulate male erectile function.
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