Spatiotemporal Regulation of the Two Atrial Natriuretic Peptide Receptors in Testis

Abstract

By interacting with a guanylyl cyclase (GC) activity-containing receptor, termed GC-A, atrial natriuretic peptide (ANP) acts as a regulator of blood pressure and fluid volume homeostasis. High expression levels of GC-A in the testis and reported effects of ANP on testosterone secretion by Leydig cells are indicative of important local functions in this organ. Here we show, based on radioligand receptor labeling and immunological approaches, that seminiferous tubules rather than Leydig cells are the predominant GC-A expression sites in the rat testis. Functional activity was proved by ANP- induced cGMP accumulation in isolated seminiferous tubules. Although ontogenetic studies revealed a massive increase in GC-A levels during sexual maturation, the so-called natriuretic peptide clearance receptor, another type of ANP receptor proposed to locally control the availability of natriuretic peptides, was found to be expressed predominantly before puberty, exceeding the level of GC-A expression at this time. Natriuretic peptide clearance receptor also shows a distinct distribution pattern surrounding the seminiferous tubules. These findings raise the possibility of novel physiological roles for ANP and cGMP in the testis related to germ cell maturation and/or the regulation of the onset of puberty and suggest that the two ANP receptors function in a coordinated manner at this target organ.

C-type natriuretic peptide regulates blood–testis barrier dynamics in adult rat testes

“…Recent studies have also shown that the effects of ANP on the endothelial TJ barrier function are also mediated via changes in the phosphorylation status of occludin and ZO-1 at the TJ site (16). More important, NPR-A (or GC-B, the receptor of ANP) was recently shown to be predominantly localized in the seminiferous tubule instead of cells in the interstitium, such as Leydig cells in rat testes (43). Different natriuretic peptides can exert differential effects on endothelial barrier function.…”

Localization and Characterization of an Orphan Receptor, Guanylyl Cyclase-G, in Mouse Testis and Sperm

“…As shown in Figs 1 and 3, the mRNA expression of mGC-G is broadly in agreement with its protein expression in sperm from round spermatids to mature sperm. In a recent study, GC-A was shown to be expressed in round and elongated spermatids in the rat testis by radioligand receptor labeling and immunological approaches; however, its expression in cauda epididymal sperm was not reported (29). Although the sea urchin sperm-receptor GC localizes to the entire length of the flagellum (30), we found that mGC-G is restricted to the midpiece of the flagellum and the head region.…”

The Role of PDE5 Inhibitors in the Treatment of Testicular Dysfunction

“…These data, demonstrating complex contraction and relaxation activities, are indicative of a major physiological role of guanylate cyclase/cGMP pathway in the regulation of tunica albuginea function related to testicular sperm transport (Middendorff et al, 2002). In addition to its role in the tunica albuginea, ANP was found to affect spermatogenesis during postnatal development (Muller et al, 2004). In fact, a male germ specific cGK-anchoring protein, designed as GKAP42 (Yuasa et al, 2000) is expressed in a stage-dependent manner in spermatocytes and round spermatids.…”

“…Thus growth regulation appears to represent an important aspect of the natriuretic peptide system (Silberbach & Roberts, 2001;Cameron & Ellmers, 2003). Considering that human spermatozoa can respond in a cGMP-dependent manner to ANP (Anderson et al, 1995) and that this peptide is capable of inducing acrosome reactions in spermatozoa (Rotem et al, 1998), there may be a probability for a role of GC-A in the regulation of the spermatozoal function (Muller et al, 2004).…”