The role of hormones, growth factors and their receptors in pituitary tumorigenesis.
Numerous factors have been shown to govern adenohypophysial cell proliferation. Human and animal models have documented that the hypothalamic trophic hormone growth hormone-releasing hormone stimulates cell proliferation, and prolonged stimulation leads to tumor formation. Similarly, lack of dopaminergic inhibition of lactotrophs and lack of feedback suppression by adrenal, gonadal or thyroid hormones are implicated, perhaps through hypothalamic stimulatory mechanisms, in pituitary adenoma formation superimposed on hyperplasia. However, most pituitary tumors are not associated with underlying hyperplasia. Overexpression of growth factors and their receptors, such as EGF, TGFalpha, EGF-R and VEGF has been identified in pituitary adenomas, and reduction of follistatin expression has been implicated in gonadotroph adenomas. Aberrant expression of members of the FGF family, an FGF antisense gene and FGF receptors have all been described in pituitary adenomas. The clonal composition of pituitary adenomas attests to the molecular basis of pituitary tumorigenesis, however, the evidence suggests that these various hypophysiotropic hormones and growth factors likely play a role as promoters of tumor cell growth in genetically transformed cells.
Ezzat
S
S
Department of Medicine, University of Toronto, and The Freeman Centre for Endocrine Oncology, Mount Sinai Hospital, Ontario, Canada. sezzat@mtsinai.on.ca
D000236:Adenoma / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004298:Dopamine / Q000502:physiology; D005246:Feedback; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D006965:Hyperplasia; D007028:Hypothalamic Hormones / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000473:pathology; D010911:Pituitary Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000502:physiology; D017978:Receptors, Growth Factor / Q000502:physiology*
D012739:Gonadal Steroid Hormones; D006133:Growth Substances; D007028:Hypothalamic Hormones; D017448:Receptors, Dopamine D2; D017978:Receptors, Growth Factor; D004298:Dopamine