Pit-1 upregulation by HMGA proteins has a role in pituitary tumorigenesis.

We have previously demonstrated that HMGA1b and HMGA2 overexpression in mice induces the development of growth hormone (GH) and prolactin (PRL) pituitary adenomas mainly by increasing E2F1 transcriptional activity. Interestingly, these adenomas showed very high expression levels of Pit-1, a transcriptional factor that regulates gene expression of GH, PRL, GHRHr and Pit-1 itself, playing a key role in pituitary gland development and physiology. Therefore, the aim of our study was to identify the role of Pit-1 overexpression in the pituitary tumour development induced by HMGA1b and HMGA2. First, we demonstrated that HMGA1b and HMGA2 directly interact with both Pit-1 and its promoter in vivo, and that these proteins positively regulate Pit-1 promoter activity, also cooperating with Pit-1 itself. Subsequently, we showed, by colony forming assays on two different pituitary adenoma cell lines, GH3 and αT3, that Pit-1 overexpression increases pituitary cell proliferation. Finally, the expression analysis of HMGA1, HMGA2 and Pit-1 in human pituitary adenomas of different histological types revealed a direct correlation between Pit-1 and HMGA expression levels. Taken together, our data indicate a role of Pit-1 upregulation by HMGA proteins in pituitary tumours.