Evidence for Production and Functional Activity of Nitric Oxide in Seminiferous Tubules and Blood Vessels of the Human Testis

Abstract

Previous studies have demonstrated that nitric oxide (NO) influences Leydig cell function. Here we provide evidence for NO production and activity in seminiferous tubules and blood vessels of the human testis. By immunohistochemistry, the soluble guanylyl cyclase (sGC), the intracellular NO receptor, and the second messenger, cyclic guanosine monophosphate (cGMP), were detected in myofibroblasts of the peritubular lamina propria in Sertoli cells, as well as in endothelial and smooth muscle cells of testicular blood vessels. Performed with isolated tubules and blood vessels, the biological activity of sGC could be proved by cGMP generation in response to treatments with the NO donor, sodium nitroprusside. The endothelial and neuronal subtypes of NO synthase (NOS) were localized immunohistochemically to the same cell types that express sGC and cGMP. In isolated tubules and vessels, the presence of endothelial NOS and neuronal NOS was confirmed by immunoblotting, and NOS activity was demonstrated by decreased cGMP production upon incubation with the NOS inhibitor L-nitro arginine methylester. These findings show that peritubular cells, Sertoli cells, and testicular blood vessels may be sites of NO production and activity, possibly involved in relaxation of seminiferous tubules and blood vessels to modulate sperm transport and testicular blood flow, respectively.

An Alternative Promoter of the Human Neuronal Nitric Oxide Synthase Gene Is Expressed Specifically in Leydig Cells

“…In previous studies the rabbit antiserum against nNOS was adsorbed with nNOS protein (20 g/ml), resulting in negative staining of the sections. 25,26 …”

Neuronal nitric oxide synthase-derived hydrogen peroxide is a major endothelium-dependent relaxing factor

“…Hence, in the mouse aorta, the effects of nonselective NOS inhibitors cannot be solely ascribed to NO release and action without considering the coparticipation of H2O2 in mediating vasodilatation. vasorelaxation; acetylcholine; antisense; knockdown NEURONAL NITRIC OXIDE (NO) synthase (nNOS) is a Ca 2ϩ / calmodulin-dependent isoform of NO synthase (NOS) constitutively expressed in neurons and in many other different tissues (17,32,36,50,57). In the cardiovascular system, nNOS is expressed in vascular smooth muscle cells (6, 7), vascular endothelium (1, 23), and cardiac myocytes (53).…”

“…vasorelaxation; acetylcholine; antisense; knockdown NEURONAL NITRIC OXIDE (NO) synthase (nNOS) is a Ca 2ϩ / calmodulin-dependent isoform of NO synthase (NOS) constitutively expressed in neurons and in many other different tissues (17,32,36,50,57). In the cardiovascular system, nNOS is expressed in vascular smooth muscle cells (6,7), vascular endothelium (1,23), and cardiac myocytes (53).…”

The Role of PDE5 Inhibitors in the Treatment of Testicular Dysfunction

“…Activation of sGC by HO-1-produced CO has resulted in increased cGMP levels . Since sGC has been found to be present in peritubular myofibroblasts, production of CO by HO-1 in the adluminal parts of Sertoli cells may trigger cGMP accumulation in peritubular lamina propria cells suggesting separation of the site of production and action of CO thereby mediating relaxation of myofibroblasts (Middendorff et al, 1997). Scipioni et al, (2005) have reported that there is expression of PDE5 in Leydig cells and peritubular cells both in prepuberal and in adult rat testis.…”