Early multipotential pituitary focal hyperplasia in the alpha-subunit of glycoprotein hormone-driven pituitary tumor-transforming gene transgenic mice.
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.
Abbud
Rula A
RA
Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Takumi
Ichiro
I
Barker
Erin M
EM
Ren
Song-Guang
SG
Chen
Dar-Yong
DY
Wawrowsky
Kolja
K
Melmed
Shlomo
S
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
D015292:Glycoprotein Hormones, alpha Subunit; D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D005640:Follicle Stimulating Hormone