Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 19 P190

SFEBES2009 Poster Presentations Endocrine tumours and neoplasia (32 abstracts)

Expression of guanylyl cyclase-B (GC-B) receptors in a range of human pituitary adenomas: evidence for a local natriuretic peptide system

I Thompson 1 , O Ansorge 2 , N Karavitaki 3 , J Wass 3 & R Fowkes 1

1Royal Veterinary College, University of London, London, UK; 2John Radcliffe Hospital, Oxford, UK; 3Oxford Centre for Diabetes, Endocrinology & Metabolism, Oxford, UK.

Several recent studies have identified Npr2 gene mutations (encoding the guanylyl cyclase B (GC-B) receptor) as causing dwarfism and achondroplasia. Npr2 null mice have a similar bone phenotype, pituitary growth hormone deficiency and female infertility. As the endogenous ligand for GC-B, C-type natriuretic peptide (CNP) is expressed at high levels in the anterior pituitary of rats and mice, we examined whether components of the natriuretic peptide system were also expressed in human pituitary tissue. A small range of pituitary adenomas were collected and analysed following transphenoidal surgery. From this series, 12 adenomas of gonadotroph (GONA) and 5 somatotroph (SOMA) origin were identified for further examination, along with 1 Cushings, 1 silent ACTH-secreting adenoma, 2 null-cell adenomas and 1 normal human pituitary sample (collected post-mortem). Total RNA was extracted and subjected to RNA clean-up and DNase treatment before performing RT-PCR with a range of intron-spanning primers specifically targeting Npr2, Nppc (CNP), Pit-1, SF-1 and L-19. Full-length Npr2 (GC-B1) was expressed in all tumours examined as well as the normal pituitary sample. No expression of GC-B2 splice variant was seen in any sample, but a few expressed low levels of truncated GC-B3. Surprisingly, only one tumor (an ACRO) expressed Nppc. All GONA tumours expressed SF-1, all ACRO tumours expressed Pit-1. Interestingly, three GONA tumours expressed Pit-1, two ACRO tumours expressed SF-1, as did a null-cell adenoma. Immunohistochemistry for GC-B protein revealed modest staining in all tumour sections examined. These findings are the first to report expression of GC-B receptor in human pituitary adenomas, suggesting these tumours may be a target for locally produced CNP. The potential therapeutic role for CNP in regulating tumor growth & hormone production remains to be investigated.

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