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This Article Full Text Full Text (PDF) Supplementary figures 1&2 All Versions of this Article: JOE-09-0189v1 203/2/215    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Thompson, I. R Articles by Fowkes, R. C PubMed PubMed Citation Articles by Thompson, I. R Articles by Fowkes, R. C

¹ Endocrine Signalling Group, Veterinary Basic Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK
² Barts and the London School of Medicine and Dentistry, Centre for Endocrinology, WHRI, Queen Mary University of London, London EC1M 6BQ, UK
³ Department of Medicine, University of Texas Health Sciences Center in San Antonio, San Antonio 78229-3900, Texas, USA
⁴ Cardiovascular and Inflammation Group, Royal Veterinary College, University of London, London NW1 0TU, UK
⁵ Laboratory for Integrated Neurosciences and Endocrinology, University of Bristol, Bristol BS1 3NY, UK

(Correspondence should be addressed to R C Fowkes; Email: rfowkes{at}rvc.ac.uk)

In the pituitary, C-type natriuretic peptide (CNP) has been implicated as a gonadotroph-specific factor, yet expression of the CNP gene (Nppc) and CNP activity in gonadotrophs is poorly defined. Here, we examine the molecular expression and putative function of a local gonadotroph natriuretic peptide system. Nppc, along with all three natriuretic peptide receptors (Npr1, Npr2 and Npr3), was expressed in both T3-1 and LβT2 cells and primary mouse pituitary tissue, yet the genes for atrial-(ANP) and B-type natriuretic peptides (Nppa and Nppb) were much less abundant. Putative processing enzymes of CNP were also expressed in T3-1 cells and primary mouse pituitaries. Transcriptional analyses revealed that the proximal 50 bp of the murine Nppc promoter were sufficient for GNRH responsiveness, in an apparent protein kinase C and calcium-dependent manner. Electrophoretic mobility shift assays showed Sp1/Sp3 proteins form major complexes within this region of the Nppc promoter. CNP protein was detectable in rat anterior pituitaries, and electron microscopy detected CNP immunoreactivity in secretory granules of gonadotroph cells. Pharmacological analyses of natriuretic peptide receptor activity clearly showed ANP and CNP are potent activators of cGMP production. However, functional studies failed to reveal a role for CNP in regulating cell proliferation or LH secretion. Surprisingly, CNP potently stimulated the human glycoprotein hormone -subunit promoter in LβT2 cells but not in T3-1 cells. Collectively, these findings support a role for CNP as the major natriuretic peptide of the anterior pituitary, and for gonadotroph cells as the major source of CNP expression and site of action.