FP39-1 INCREASED EXPRESSION OF THE STEM CELL MARKER SOX2 IN THE PITUITARY GLANDS OF MICE WITH CONGENITAL HYPOPITUITARISM

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP39-Pituitary
Basic
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:45 AM
Room 133 (Moscone Center)

Poster Board MON-114
Claudia Chang*1, CInthya S Cirqueira2, Ibere Cauduro Soares3, Sally Ann Camper4, Ricardo Viera Araujo5 and Luciani Renata Silveira Carvalho6
1Hospital das Clinicas University of Sao Paulo, São Paulo, Brazil, 2Hospital das clinicas University of, São Paulo, Brazil, 3Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, 4Univ MI Med Sch, Ann Arbor, MI, 5HC. FMUSP, S?o Paulo, Brazil, 6Hosp das Clinicas, Sao Paulo, Brazil
Background: Tissue stem cells are characterized by their ability to proliferate, self-renew, differentiate,  and regenerate the tissue after cell loss.  Although stem cells are reported to be involved in replenishing normal cell turnover and in homeostatic regulation of the pituitary gland, little is known about their pattern of expression in hypopituitarism.  The Ames dwarf (Prop1df) and Snell dwarf (Pou1f1dw) mice are spontaneous mutants with hypopituitarism due to pituitary transcription factor mutations.  Prop1df/df present at birth with pituitary dysmorphology, while Pou1f1dw/dw pituitaries have a normal appearance.  Both mutants evolve to obvious hypoplasia by the seventh postnatal day (P7), and exhibit reduced cell proliferation and increased cell death.  The Cga knockout mice (Cgako/ko) lack the alpha subunit of the glycoprotein hormones, and have hypopituitarism associated with hyperplasia.  Objective: We aimed to analyze the expression pattern of Sox2 in animal models with different causes of hypopituitarism. Materials and Methods: We collected pituitaries from the Ames (Prop1df/df), Snell (Pou1f1dw/dw) and Cga gene knockouts and their normal littermates at P0 (birth day), P7, 4 and 8 weeks (W) of life. Sox2 expression was analyzed by RT-Qpcr, normalized by Gapdh, Ppia, Hprt, B2m as endogen genes and immunohistochemistry (IHC). Results: SOX2 expression is normally detected in the cells that line the remnants of Rathke’s cleft and in isolated hormone-negative cells in the adenohypophisis. Our IHC analyses detected SOX2 expression in Prop1df/df, Pou1f1dw/dw, Cgako/ko in marginal zone in both mutants and wild type, in all periods evaluated.  The level of Sox2 mRNA was unchanged in the pituitaries of Cgako/ko mice at 4 and 8W relative to wild type.  In contrast, Sox2 mRNA levels were elevated in Pou1f1dw/dw pituitaries at 4 and 8W.  The Prop1df/df mutants have higher levels of Sox2 expression in adults (8W), but levels were lower than normal at the end of the first wave of pituitary growth (P7 and 4W). Conclusions: Mutations in the Prop1 and Pou1f1 genes induce increased Sox2 expression, but Cga mutations have no detectable effect on Sox2 expression at the ages examined. The hypopituitarism in Prop1 and Pou1f1 mutants arises from failed cell differentiation, but Cga mutants have extensive hyperplasia.  Thus, elevated Sox2 expression is associated with hypopituitarism caused by developmental arrest.

Nothing to Disclose: CC, CSC, ICS, SAC, RVA, LRSC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Fundação de amparo da pesquisa do estado de São Paulo, processo 2010/11611-2
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