title: Early multipotential pituitary focal hyperplasia in the alpha-subunit of glycoprotein hormone-driven pituitary tumor-transforming gene transgenic mice.
abstract: Pituitary tumor-transforming gene (PTTG), a securin protein isolated from pituitary tumor cell lines, is highly expressed in invasive tumors and exhibits characteristics of a transforming gene. To determine the role of PTTG in pituitary tumorigenesis, transgenic human PTTG1 was targeted to the mouse pituitary using the alpha-subunit of glycoprotein hormone. Males showed plurihormonal focal pituitary transgene expression with LH-, TSH-, and, unexpectedly, also GH-cell focal hyperplasia and adenoma, associated with increased serum LH, GH, testosterone, and/or IGF-I levels. MRI revealed both pituitary and prostate enlargement at 9-12 months. Urinary obstruction caused by prostatic hyperplasia and seminal vesicle hyperplasia, with renal tract inflammation, resulted in death by 10 months in some animals. Pituitary PTTG expression results in plurihormonal hyperplasia and hormone-secreting microadenomas with profound peripheral growth-stimulatory effects on the prostate and urinary tract. These results provide evidence for early pituitary plasticity, whereby PTTG overexpression results in a phenotype switch in early pituitary stem cells and promotes differentiated polyhormonal cell focal expansion.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
authors.forename: Rula A
authors.initials: RA
authors.lastname: Abbud
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takumi
authors.forename: Erin M
authors.initials: EM
authors.lastname: Barker
authors.forename: Song-Guang
authors.initials: SG
authors.lastname: Ren
authors.forename: Dar-Yong
authors.initials: DY
authors.lastname: Chen
authors.forename: Kolja
authors.initials: K
authors.lastname: Wawrowsky
authors.forename: Shlomo
authors.initials: S
authors.lastname: Melmed
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005640:Follicle Stimulating Hormone / Q000097:blood; D015292:Glycoprotein Hormones, alpha Subunit / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010900:Pituitary Diseases / Q000378:metabolism*; D010902:Pituitary Gland / Q000473:pathology; D064249:Securin; D014566:Urogenital System / Q000473:pathology
chemical_list: D015292:Glycoprotein Hormones, alpha Subunit; D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D005640:Follicle Stimulating Hormone