Mechanisms of Hormone Action

Expression of the Receptor Guanylyl Cyclase C and Its Ligands in Reproductive Tissues of the Rat: A Potential Role for a Novel Signaling Pathway in the Epididymis

Abstract

Guanylyl cyclase C is a membrane associated form of guanylyl cyclase and serves as the receptor for the heat stable enterotoxin (ST) peptide and endogenous ligands guanylin, uroguanylin and lymphoguanylin. The major site of expression of GC-C is the intestinal epithelial cell, though various studies have shown that GC-C is also expressed in extra intestinal tissue such as the kidney, airway epithelium, perinatal liver, stomach, brain and adrenal glands. Binding of ligands to GC-C leads to accumulation of intracellular cGMP, the activation of protein kinase G and A and phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel which regulates salt and water secretion. Here, we have studied the expression of GC-C and its ligands in various tissues of the reproductive tract of the rat. Using reverse transcriptase and the polymerase chain reaction, we demonstrate the presence of GC-C, uroguanylin, and guanylin mRNA in both and in female reproductive organs. Western blot analysis using a monoclonal antibody to GC-C revealed the presence of differentially glycosylated forms of GC-C in the caput and cauda epididymis. Exogenous addition of uroguanylin to epididymal minces resulted in cGMP accumulation, suggesting an autocrine or endocrine activation of GC-C in this tissue. Immunohistochemical analyses demonstrated expression of GC-C in the tubular epithelial cells of both the caput epididymis and cauda epididymis. Our results therefore suggest that the GC-C signaling pathway could converge on CFTR in the epididymis and perhaps control fluid and ion balance for optimal sperm maturation and storage in this tissue.