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| Author(s): |
Leonardo de Oliveira Mendes
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2014-03-18 |
| Examining board members: |
Francisco Eduardo Martinez;
Glaura Scantamburlo Alves Fernandes;
Luis Antonio Justulin Junior;
Patrick Vianna Garcia;
Silvana Gisele Pegorin de Campos
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| Advisor: | Wellerson Rodrigo Scarano; Francisco Eduardo Martinez |
| Abstract | |
Ethanol induces reproductive damages, directly in the tissues or indirectly by hormonal imbalance. Prostate, a hormone-dependent gland, is susceptible to effects caused by ethanol. Emerging evidences assign to testosterone an anti-inflammatory role, with growing interest in the action of hormone therapy on the effects of ethanol. Therefore, the current research aimed to assess the effects of hormone therapy with testosterone on the ethanol consumption: 1) in tissue and plasma hormone assays, histopathology and immunolocalization and expression of hormone receptors (manuscript I); plasma levels and expression of pro and anti-inflammatory cytokines (manuscript II) in the ventral prostate of UChB rats (ethanol-preferring rat). UChB rats aged 90 days were divided into two experimental groups (n=20): C: drinking water only and EtOH: drinking 10% (v/v) ethanol at > 2 g/kg body weight/day + water. At 150 days of age, 10 rats from each group received subcutaneous injections of testosterone cypionate (5mg/kg body weight) diluted in corn oil every other day during 4 weeks, constituting T and EtOH+T, while the remaining animals (10/group) received corn oil as vehicle. All animals were euthanized at 180 days old by decapitation. Blood was collected to obtain plasma hormone and cytokines concentrations and ventral prostate was dissected, weighted and processed. Prostate sections were stained with hematoxylin and eosin, Gomori¿s reticulin and toluidine blue. The following techniques were performed: radioimmunoassay to plasma concentrations of testosterone, dihydrotestosterone (DHT), estradiol and intraprostatic testosterone, immunohistochemistry to Ki-67, AR, ER?, ER?, DACH-1, TGF-?1, pSmad 2, e-cadherin e ?-actinin, western blot to AR, ER?, ER?, DACH-1, PAR4, IL-6 IL-10, TNF? and TGF-?1 and elisa to plasma concentrations of IL-6, IL-10, TNF-? and TGF-?1. Testosterone therapy increased the ventral prostate weight. There were reducing of epithelial compartment and increasing of luminal compartment in the EtOH and hormonal therapy was able to reverse this pattern. Stroma compartment of EtOH showed thin and sparse reticular fiber bundles with rupture of smooth muscle cell layer. Inflammatory foci metaplasia, inflammatory reactive atypia, loss of cell-cell adhesion and increasing of degranulated mast cells were frequent in EtOH and absent in EtOH+T. Testosterone and ethanol did not alter the proliferation rate, but high expression of PAR4 was shown in EtOH. There was increasing of plasma and intraprostatic testosterone and plasma DHT in T and EtOH+T and decreasing of estradiol in EtOH+T. The T and EtOH+T exhibited increasing of plasma TNF? and TGF-?1, without differences regarding to IL-6 and IL-10. AR, ER?, DACH-1 and IL-6 expressions were similar among the experimental groups, differently from ER?, TNF? and TGF-?1, which decreased after hormonal therapy. Our results show that ethanol was able to induce the emergence of inflammatory foci, besides suppress the immunorreactivity to e-cadherin and ?-actinin. Testosterone was able to reverse these effects, downregulating ER?, TGF-?1, TNF? and NFR2, showing to be promising in the treatment of alcohol-related disorders (AU) | |