Oestrogen imprinting causes nuclear changes in epithelial cells and overall inhibition of gene transcription and protein synthesis in rat ventral prostate

Autor(es)

Augusto, T. M. ^[1] ; Bruni-Cardoso, A. ^[1] ; Damas-Souza, D. M. ^[1] ; Zambuzzi, W. F. ^[2] ; Kuehne, F. ^[1] ; Lourenco, L. B. ^[1] ; Ferreira, C. V. ^[2] ; Carvalho, H. F. ^[1]

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Dept Anat Cell Biol Physiol & Biophys, Inst Biol, BR-13083863 Campinas, SP - Brazil

^[2] State Univ Campinas UNICAMP, Dept Biochem, Inst Biol, BR-13083863 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF ANDROLOGY; v. 33, n. 5, p. 675-685, OCT 2010.
• Citações Web of Science: 4

Resumo

Oestrogen exposure during the early post-natal period affects male growth, physiology, and susceptibility to disease in adult life. The prostate gland is susceptible to this oestrogen imprinting, showing a reduced expression of the androgen receptor and inability to respond to androgen stimulus. In this context, we decided to study key signalling regulators of ventral prostate (VP) functioning after early postnatal exposure to high-dose oestrogen. Our results showed a decrease of mTOR phosphorylation and its direct downstream target 4EBP. It is known that mTOR-induced signalling is a pivotal pathway of cell metabolism, which is able to control gene transcription and protein synthesis. We then decided to investigate other indicators of a reduced metabolism in the oestrogenized prostate, and found that the luminal epithelial cells were shorter, less polarized and had smaller nuclei containing more compacted chromatin, suggesting that a general mechanism of regulating gene expression and protein synthesis could be installed in the epithelium of the oestrogenized VP. To evaluate this idea, we analysed nucleolar morphology, and measured the amount of ribosomes and the level of methylation of the 45S ribosomal RNA promoter region. These data indicated that the nucleolus was dismantled and that the methylation at the 45S promoter was increased (similar to five-fold). Taken together, the results support the idea that the oestrogenized prostate maintains a very low transcriptional level and protein turnover by affecting canonical signalling pathways and promoting nuclear and nucleolar changes. (AU)

• Processo FAPESP: 05/02601-5 - Mecanismos epigenéticos de regulação da expressão do receptor de andrógenos na próstata
• Beneficiário: Hernandes Faustino de Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/53003-9 - Investigação da função da proteína tirosina fosfatase de baixa massa molecular (LMW-PTP) na adesão de osteoblastos e formação óssea
• Beneficiário: Willian Fernando Zambuzzi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado