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Analysis of SOX2 expression during puberty and its relation to terminal differentiation and hormonal production in animals with spontaneous mutation in the Prop1 gene

Grant number: 16/16493-4
Support type:Scholarships in Brazil - Master
Effective date (Start): June 01, 2017
Effective date (End): May 31, 2019
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Luciani Renata Silveira de Carvalho
Grantee:Juliana Moreira Silva
Home Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The pituitary gland produces and secretes hormones related to growth, fertility, lactation and stress response. Its development is similar in all vertebrates and is controlled by several transcription factors. The initial phases of the anterior pituitary gland development is regulated by many transcription factors, including HESX1, GLI2, OTX2, LHX3, LHX4, SOX2 and SOX3 as well as the transcription factors PROP1 and POU1F1 (PIT-1) that are involved in cell terminal differentiation. These factors participate in a cascade of events responsible for the formation of pituitary hormones (LH, FSH, TSH, GH and PRL). In the absence of one or more transcription factor, it is observed a deficiency of hormones produced by the pituitary gland. The Ames strain, a mice lineage with spontaneous mutation in the Prop1 gene, is extensively used as an animal model to study congenital hypopituitarism. The absence of PROP1 in the Ames mice causes an accumulation of the pituitary stem cell/progenitor marker SOX2 during periods corresponding to birth (P0), the first wave of growth (P7), and adulthood (8 weeks). However, during puberty (4 weeks) of Ames mice, it is observed a reduction of Sox2 associated with the elevation in the expression levels of genes coding pituitary hormones in relation to wildtype animals. This data suggests that the pituitary axis is recovered by a still unknown mechanism that could be compensating PROP1 absence. This study aims to evaluate and confirm the pattern of Sox2 and pituitary hormones expression and also to characterize the factors involved in the onset of cell differentiation and hormonal expression during the pubertal period in the Ames model. (AU)

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