PubMed · 3026586
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J Tourniaire, M Fèvre-Montange, A Abou Samra, H Dechaud. 1986. [Melatonin and the corticotropic function].. https://pubmed.ncbi.nlm.nih.gov/3026586/
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The high mobility group As (HMGAs) belong to a family of nonhistone nuclear proteins that orchestrate the assembly of nucleoprotein complexes. Through a complex network of protein-DNA and protein-protein interaction, they play important roles in gene transcription, recombination, and chromatin structure. This protein family is involved, through different mechanisms, in both benign and malignant neoplasias. We have recently reported that transgenic mice carrying the Hmga1 or Hmga2 genes under transcriptional control of the cytomegalovirus promoter develop pituitary adenomas secreting prolactin and growth hormone. We have shown that the mechanism of the HMGA2-induced pituitary adenoma is based on the increased E2F1 activity. The expression profile of mouse normal pituitary glands and adenomas induced in HMGA transgenic mice revealed an increased expression of the ccnb2 gene, coding for the cyclin B2 protein, in the neoplastic tissues compared with the normal pituitary gland. Here, we show, by electrophoretic mobility shift assay and chromatin immunoprecipitation, a direct binding of HMGA proteins to the promoter of ccnb2 gene, whereas luciferase assays showed that HMGAs are able to up-regulate ccnb2 promoter activity. Finally, we report an increased CCNB2 expression in human pituitary adenomas of different histotypes that is directly correlated with HMGA1 and HMGA2 expression. Because cyclin B2 is involved in the regulation of the cell cycle, these results taken together indicate that HMGA-induced cyclin B2 overexpression gives an important contribution to experimental and human pituitary tumorigenesis.
There has been considerable interest in the relationship between hormone-secreting endocrine cells (HSEC) and their microvessels (MVN) in human pituitary gland. However, microcirculatory networks have rarely been studied in three dimensions (3D). Therefore, this study was designed to visualize and to reveal the relationship between hormone secreting endocrine cells and their microvessel environment including vascular endothelial cells in 3D using rat pituitary glands under various experimental conditions by confocal laser scanning microscopy (CLSM). By CLSM, the 3D distributions of MVN were visualized and revealed a relationship between HSEC and MVN in experimental pituitary glands and human pituitary adenomas. Therefore, 3D reconstructed imaging by CLSM is a useful technique with which to investigate the microvessel environment of hormone-secreting cells and has the potential to reveal dynamic hormone-secreting pathways.
Angiogenesis, which is the formation of new blood vessels from preexisting capillaries, plays an important role in tumor growth and metastasis. In this review, the focus is on angiogenesis in pituitary adenomas. Angiogenesis of pituitary adenomas has been assessed by studying tumor microvessel density using specific immunohistochemical markers to clarify the relationship between angiogenesis and tumor behavior. Unlike other organs, pituitary adenomas have significantly lower vascular densities as compared to nontumorous adenohypophysis, suggesting that the lack of significant angiogenesis may play a role in the slow pace of pituitary tumor growth and rarity of metastases. In addition, the relationship between microvessel density and various factors in pituitary adenomas is reviewed, including tumor types, age and sex, invasiveness, malignancy, several proliferative markers (MIB-1 or Ki-67). However, further studies will be needed, since many studies have reached opposite conclusions. Angiogenesis is a complex multistep process and several factors are found to be involved in each step of neovascularization, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and various other cytokines. VEGF and bFGF (or FGF-2), which are the most potent angiogenesis inducers among them, have been studied by immunohistochemistry, in situ hybridization, or in vitro studies in normal or adenomatous pituitaries and these results are also discussed in this review.