ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 11 P497

Differential expression of neurogenins by human pituitary adenomas

A Fratticci1, R Padronetti1, F Giangaspero2, L Ventura3, M Piccirilli4, V Esposito2, A Gulino5, E Alesse1 & ML Jaffrain-Rea1

1Dept of Exp. Medicine, University of L’Aquila, L’Aquila, Italy; 2Neuromed Institute, IRCCS, Pozzili, Italy; 3Pathology, San Salvatore Hospital, L’Aquila, Italy; 4Dept of Neuroscience, University La Sapienza, Rome, Italy; 5Dept of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.

The beta-HLH transcription factors NeuroD1 and ASH1 are frequently expressed by pituitary adenomas, both being present in all corticotroph, most clinically non-secreting (CNS) and a subset of GH and/or PRL-secreting adenomas. We wished to investigate the expression of the related beta-HLH factors neurogenins (Ngn) 1, 2 and 3 in the pituitary (n=4) and in a series of pituitary adenomas (n=45). RT-PCR was performed at different amplification cycles (up to 45) in all cases. Ngn1 was undetectable in all samples. Ngn2 transcripts were detected in 56% of pituitary adenomas by RT-PCR (33/45) and up to 73% after Southern blotting (33/45). Low levels of Ngn2 transcripts were also detected in some normal pituitary samples. Preliminary data from immunohistochemistry are confirming Ngn2 protein expression and its nuclear localization in pituitary adenomas and a subset of normal pituitary cells. Ngn3 transcripts were undetectable in normal pituitaries and present in a subset of pituitary adenomas: 25% by RT-PCR (11/44), and 30% after Southern blotting (12/40). Overall, Ngn2/3 expression did not significantly correlate with tumour aggressiveness or with NeuroD1/ASH1 expression at a transcriptional level. Neither was their expression significantly influenced by tumor phenotype: Ngn2 was detected in all ACTH-secreting adenomas (100%) and in most CNS and PRL/GH/TSH-secreting adenomas too (67% and 74%, respectively), whereas Ngn3 was detected in a subset of all adenoma phenotypes (25% of ACTH-, 25% of CNS and 37% of GH/PRL/TSH-secreting adenomas, respectively). The expression of Ngn2 and to a lesser extent of Ngn3 in pituitary samples is consistent with their ontogenetic role in other neuroendocrine (NE) tissues, such as neural crest (Ngn2) and gastroenteropancreatic NE cells (Ngn3), and suggest a possible role in pituitary ontogenesis too. At the moment, there is no evidence for a significant role Ngn2/3 in pituitary tumorigenesis or in NeuroD1/ASH1 regulation.

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