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

• Grant number: 09/15317-4
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: November 01, 2009
• End date: October 31, 2011
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Hernandes Faustino de Carvalho
• Grantee: Hernandes Faustino de Carvalho
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Estrogen 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 estrogen imprinting, showing a reduced expression of the androgen receptor and inability to respond to androgen stimulus. In this context, we decided to study key signaling regulators of ventral prostate functioning after early postnatal exposure to high-dose estrogen. Our results showed a decrease of mTOR phosphorylation and its direct downstream target 4EBP. It is known that mTOR-induced signaling 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 estrogenized 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 estrogenized VP. In order to evaluate this idea, we analyzed 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, the methylation at the 45S promoter was increased (~5-fold), and that the absolute amount of 18S rRNA was reduced to less than 1% of the control. Taken together, the results obtained here support the idea that the estrogenized prostate maintains a very low transcriptional level and protein turnover by affecting canonical signaling pathways and promoting nuclear and nucleolar changes. (AU)