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Human Molecular Genetics, 2001, Vol. 10, No. 11 1141-1153
© 2001 Oxford University Press

Persistent Prop1 expression delays gonadotrope differentiation and enhances pituitary tumor susceptibility

Lisa J. Cushman1, Dawn E. Watkins-Chow1, Michelle L. Brinkmeier1, Lori T. Raetzman1, Amy L. Radak1, Ricardo V. Lloyd2 and Sally A. Camper1,+

1Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109-0638, USA and 2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA

The ‘paired’-like homeodomain transcription factor Prop1 is essential for the expansion of the pituitary primordia and for the differentiation and/or function of the hormone-producing cells of the anterior pituitary gland. Prop1 expression is normally extinguished before transcription of most differentiation markers is initiated. We report that constitutive expression of Prop1 interferes with anterior pituitary cell differentiation and increases the susceptibility for pituitary tumors. The terminal differentiation of pituitary gonadotropes is delayed, resulting in transient hypogonadism and a delay in the onset of puberty. Thyrotrope differentiation occurs normally, but thyrotrope function is impaired resulting in mild hypothyroidism. Aged mice exhibit defects consistent with misregulation of pituitary cell proliferation, including adenomatous hyperplasia with the formation of Rathke’s cleft cysts and tumors. Thus, silencing Prop1 is important for normal pituitary development and function. These data suggest that gain-of-function mutations in PROP1 could contribute to the most common human pituitary endocrinopathies and tumors.

+ To whom correspondence should be addressed at: 4301 MSRB III, 1500 West Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 48109-0638, USA. Tel: +1 734 763 0682; Fax: +1 734 763 7672; Email: scamper@umich.edu


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