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.
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.
Jaleel
Mahaboobi
M
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.
London
Roslyn M
RM
Eber
Sammy L
SL
Forte
Leonard R
LR
Visweswariah
Sandhya S
SS
D000818:Animals; D000911:Antibodies, Monoclonal; D006152:Cyclic GMP / Q000096:biosynthesis; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004822:Epididymis / Q000201:enzymology*; D005260:Female; D005768:Gastrointestinal Hormones / Q000235:genetics; D015870:Gene Expression; D006162:Guanylate Cyclase / Q000235:genetics* / Q000502:physiology*; D007150:Immunohistochemistry; D008024:Ligands; D008297:Male; D045265:Natriuretic Peptides; D009928:Organ Specificity; D010455:Peptides / Q000235:genetics; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D005768:Gastrointestinal Hormones; D008024:Ligands; D045265:Natriuretic Peptides; D010455:Peptides; D012333:RNA, Messenger; D018000:Receptors, Peptide; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C072685:guanylin; C084362:uroguanylin; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D006152:Cyclic GMP