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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: INTERNATIONAL JOURNAL OF ANDROLOGY; v. 33, n. 5, p. 675-685, OCT 2010.
Web of Science Citations: 4
Abstract

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)

FAPESP's process: 05/02601-5 - Epigenetic mechanisms in the regulation of androgen receptor expression in the prostate
Grantee:Hernandes Faustino de Carvalho
Support Opportunities: Regular Research Grants