Acromegaly pathogenesis and treatment

GH transcription and somatotroph proliferation are induced by cAMP acting through CREB (). SRIF inhibits cAMP and CREB activity (S43) to suppress GH secretion. Pituitary CDKs likely exhibit overlapping functions in G1 cell-cycle progression. Somatotroph mitogenic factors include POU1F1, GHRH, and GNAS as well as endocrine hormones. Mitogenic constraints include SRIF and tumor suppressor genes, including MEN1. Cell-cycle progression through G/S is mediated by CDKs that phosphorylate Rb to release E2F proteins that drive DNA synthesis. In somatotroph tumors, the cAMP pathway may be constitutively activated. Furthermore, HMGA2 and PTTG, overexpression, and CDK inhibitor loss have been shown to result in experimental pituitary tumorigenesis. Chromosomal instability, DNA damage, and senescence, hallmarks of GH-secreting adenomas, may act to constrain malignant transformation of somatotroph tumors. Modified with permission from the Journal of molecular endocrinology (ref. S44, S45; copyrighted by the Society for Endocrinology).

Publication

Acromegaly pathogenesis and treatment. (2009) Shlomo Melmed. J Clin Invest. 2009 Nov 2;119(11):3189-3202. Figure: F4. All organisms Danio rerio Homo sapiens

Disease mentions