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This Article Full Text Full Text (PDF) All Versions of this Article: 67/6/1975    most recent biolreprod.102.006445v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jaleel, M. Articles by Visweswariah, S. S. Search for Related Content PubMed PubMed Citation Articles by Jaleel, M. Articles by Visweswariah, S. S. Agricola Articles by Jaleel, M. Articles by Visweswariah, S. S.

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 Epididymis¹

^a Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India ^b Truman Veterans Affairs Medical Center and Department of Pharmacology, School of Medicine, University of Missouri, Columbia, Missouri 65212

Guanylyl cyclase C (GC-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, although GC-C is also expressed in extraintestinal 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 kinases G and A, and phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that regulates salt and water secretion. We examined 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 demonstrated the presence of GC-C, uroguanylin, and guanylin mRNA in both male and 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 minced epididymal tissue 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 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.

¹ This work was supported by a grant under the India-Japan Inter-Governmental Science and Technology Cooperation program funded by the Department of Science and Technology, Government of India. S.S.V. was the recipient of a Short Term Associateship funded by the Department of Biotechnology, Government of India.

² Correspondence. FAX: 91 80 3600999; sandhya{at}mrdg.iisc.ernet.in

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