The pituitary gland, as a neuroendocrine organ, weighs only 0.6g, but its complex and wide range of important functions, from growth, development, reproduction, metabolic homeostasis, endocrine environment stability to aging, affects human life, which, together with the regulatory influence of hypothalamus and target gland hormones, makes the research on the pathogenesis of pituitary adenoma lack of novel understanding.
With the development of molecular genetics theory and technology and molecular biology, the research on the pathogenesis of pituitary adenoma has made breakthrough progress. The process of pituitary adenoma formation involves chromosomal abnormalities, cell proliferation, abnormal signal transduction, genetic abnormalities, growth of adherent vessels, etc. Although the pathogenesis of pituitary adenoma is not very clear, the process of abnormal expression of genes, participation of multiple cytokines and abnormal cell proliferation is basically recognized by everyone and a consensus has been reached.
(A) Chromosomal abnormalities in pituitary adenoma Mark et al. reported eight cases of chromosomal analysis of pituitary adenoma in the 1970s. In the following 30 years or so, a large number of experimental results have been reported from all over the world, confirming the presence of chromosomal abnormalities in pituitary adenoma, indicating a very strong correlation between chromosomal abnormalities and the development of pituitary adenoma. Experimental confirmation of abnormal chromosomal findings include.
(ii) Clonal origin of pituitary adenomas In the 1990s, clonal analysis of pituitary adenomas was initiated based on the Leonization hypothesis, and the X-linked alleles selected were the HPRT (hypoxanthine phosphoribosyltransferase) and PGK (phosphoglucose kinase) genes.
By using X-chromosome non-activating type analysis, Herman and Alexander et al. demonstrated that pituitary adenomas occur monoclonal to each other, suggesting that this may be caused by genetic mutations in primitive stem cells leading to cell proliferation, a theory that is now widely accepted.
(iii) Abnormal signaling pathways Abnormal signaling pathways can cause cell overproliferation, infiltration and metastasis. A variety of experiments have confirmed that mutations in Gsa play an important role in the development of GH adenomas, thus confirming that abnormal signaling pathways are one of the causes of pituitary adenoma development. The low incidence of pituitary PRL adenomas, ACTH adenomas, and TSH adenomas may be due to the fact that the hypothalamic releasing hormone that regulates the secretion of these hormones does not act through Gsa, but through other types of G proteins.
(iv) Genetic alterations in pituitary adenomas Dozens of proto-oncogenes and oncogenes have been identified. The close correlation between the Gsa gene and GH adenomas is clearer and is due to point mutations leading to mutations in the Gs protein a subunit (Gsa).
The Gsa gene, an approximately 20 Kb long base sequence consisting of 13 exons and 12 introns, is a subunit of the Gs protein a. The Gs protein is a member of the G protein family whose function is to transmit stimulatory signals from cell surface receptors to the catalytic unit of adenylate cyclase to promote the synthesis of cyclic adenosine monophosphate (cAMP). Since cAMP is dependent on the secretion of growth hormone, Gs proteins are closely related to the secretion of GH.