Differential expression of neurogenins and NeuroD1 in human pituitary tumours

Basic helix-loop-helix (bHLH) transcription factors are involved in neuroendocrine cell growth and differentiation. Though NeuroD1 is viewed as corticotroph specific, its overexpression in non-corticotroph pituitary adenomas (PAs) may reflect the activation of molecular pathways involving other bHLH factors, like neurogenins. To search for neurogenin-NeuroD1 molecular pathways in the human normal and tumoural pituitary. Fifty-one PAs--22 clinically non-secreting (CNS) and 29 secreting respectively--and normal human pituitaries (NP) were studied for NeuroD1 and neurogenins (Ngn1, Ngn2 and Ngn3) gene expression by RT-PCR and quantitative real-time RT-PCR (qRT-PCR). Immunohistochemistry for Ngn2/3 was performed in some cases. NeuroD1, Ngn2, Ngn3 and Ngn1 were observed in up to 84.3, 76.5, 30.4 and 9.1% of PA respectively, only NeuroD1 and Ngn2 being frequently overexpressed when compared with NP. Whereas NeuroD1 expression was higher in corticotroph and CNS adenomas (P=0.0001 versus Pit-1-dependent PA), Ngn2 expression was higher in secreting PA, especially in Pit-1-dependent PA (P=0.007 and P=0.0006 versus CNS respectively). Pit-1-dependent PA which received pre-operative pharmacological treatment expressed higher Ngn2 levels than untreated cases (P=0.025). Nuclear Ngn2 was observed in NP and in most PA, especially ACTH- and GH-secreting adenomas. Nuclear Ngn3 was observed in a minority of secreting PA. Ngn2 is normally expressed in the anterior pituitary and frequently expressed in PA, but does not account for NeuroD1 overexpression where present. Owing to their low and inconstant expression, the biological significance of Ngn1/3 in the adult pituitary is uncertain.