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

Endocrine Abstracts (2011) 25 P245

Evaluation of the interaction of phosphodiesterases 2A and 4A5 with the aryl hydrocarbon receptor interacting protein in pituitary cells

Carole Lennox, Giampaolo Trivellin & Marta Korbonits

Barts and the London School of Medicine and Dentistry, London, UK.

Background: Aryl hydrocarbon receptor interacting protein (AIP) mutations have been identified in ~15% of patients with familial isolated pituitary adenomas (FIPA). In addition, dysregulation of the cyclic adenosine monophosphate (cAMP) signalling pathway has been identified in both syndromic and sporadic somatotropinomas. While crosstalk between these two systems is known to occur, the exact mechanism of interaction remains elusive. The identification of direct binding between AIP and two cAMP-hydrolysing phosphodiesterases PDE2A and PDE4A5 may provide a starting point to explore this relationship (1, 2).

Aims and objectives: To investigate the presence of PDE2A and PDE4A4 in pituitary tumours. To assess whether overexpression of AIP, PDE4A5 and PDE2A affects their binding partner’s expression.

Methods: Presence of PDE2A and PDE4A4 in pituitary tumour cDNA samples was evaluated by RT-PCR. Rodent pituitary somatomammotroph cell line (GH3) were transiently transfected with wild type AIP, PDE2A, PDE4A5, mutant PDE4A5 and empty vector. Expression of AIP, PDE2A and PDE4A5 was assessed by RT-PCR and western blot.

Results: PDE2A and PDE4A4 was found to be present within pituitary adenomas. There was no significant difference in PDE2A and PDE4A4 expression between tumour subtypes and normal pituitary samples. There was no significant effect of AIP, PDE2A and PDE4A5 transfection on the cellular levels of their binding partners.

Discussion: AIP binding partners are present in sporadic pituitary adenomas but there was no difference in PDE2A and PDE4A4 expression in pituitary adenomas types or normal pituitary. Increased levels of AIP, PDE2A and PDE4A5 did not alter the expression of each other therefore different approaches are needed for the identification of possible tumorigenic mechanism involving these proteins.

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