RESUMO
Bisphenol A (BPA) and cadmium (Cd) are environmental pollutants that are implicated in potential reproductive effects, including damage to the prostate gland. Their action during puberty requires analysis to determine the relationship of these compounds with the testosterone peak that occurs during this phase. This study evaluated whether exposure to BPA and Cd during puberty can cause changes in the morphology, proliferation and cell death and androgen receptor (AR) immunostaining of the ventral prostates of normal and castrated male gerbils (Meriones unguiculatus), considering an acute exposure to the chemicals and evaluation after short (52d) and long (120d) periods. Generally, morphometric-stereological results demonstrated that administration of BPA and Cd (individually or in combination) increased epithelial height, smooth muscle layer (SML) thickness and nuclear area and perimeter, and that these parameters were reduced in castrated animals. In addition, these groups showed important inflammatory processes but not prostate lesions. The proliferation/death rates of prostatic cells obtained by PCNA and TUNEL immunostaining demonstrated increased cell death in the 52d groups; in contrast, the gland acquired a more proliferative nature in the 120d groups. AR immunostaining showed that BPA and Cd compounds interact with ARs in different ways depending on the evaluated period and the hormonal profile of the animal. We conclude that BPA and cadmium are important agents in changing the morphology, proliferation and death of prostatic cells, in addition to interacting with ARs in different patterns. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 48-61, 2017.
Assuntos
Compostos Benzidrílicos/toxicidade , Cádmio/toxicidade , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Estrogênios não Esteroides/toxicidade , Fenóis/toxicidade , Próstata/patologia , Androgênios/farmacologia , Animais , Fragmentação do DNA/efeitos dos fármacos , Gerbillinae , Imuno-Histoquímica , Masculino , Orquiectomia , Próstata/efeitos dos fármacos , Receptores Androgênicos/efeitos dos fármacos , Testosterona/sangueRESUMO
The female prostate is a functionally active gland in several mammalian species, including humans and rodents. Investigations of prostate morphophysiology during the phases of the oestrous cycle have shown that the female prostate is influenced by fluctuations in serum concentrations of oestradiol (E2) and progesterone (P4). The aim of the present study was to evaluate the effect of combined prolonged administration of E2 and P4 on the prostate in ovariectomised female gerbils. Ovariectomy caused atrophy and decreased glandular secretory activity. Administration of E2 and P4 (0.1mgkg(-1) diluted in 0.1mL of mineral oil, every 48h over 30 days) resulted in a recovery of overall prostate structure, as evidenced by increased epithelial height, mass and prostatic secretory activity, without leading the appearance of significant lesions. Evaluation of androgen receptor (AR) expression revealed increased immunoreactivity in the E2+P4-treated group. Immunostaining for oestrogen receptor (ER) α was decreased in the castrated groups, but increased in the group subjected to hormone treatment. There were no significant differences in ERß immunoreactivity among the groups. Assessment of cell proliferation revealed greater immunoreactivity in the treated group. Together, the results indicate that the interaction between E2 and P4 may be responsible for maintaining female prostate gland histophysiology.
Assuntos
Estradiol/farmacologia , Terapia de Reposição de Estrogênios , Ovariectomia , Progesterona/farmacologia , Próstata/efeitos dos fármacos , Animais , Atrofia , Proliferação de Células/efeitos dos fármacos , Estradiol/sangue , Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/metabolismo , Feminino , Gerbillinae , Masculino , Progesterona/sangue , Próstata/metabolismo , Próstata/patologia , Receptores Androgênicos/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Testosterona/sangue , Fatores de TempoRESUMO
The female prostate is a differentiated organ found in several mammal species, including humans and rodents. This gland has been related to important functions on female reproductive biology. Although the factors, which regulate prostate's development and activity are not well known, its functionality has been related to steroid hormones. It is well established that cyclic changes of estradiol and progesterone levels promote histophysiological adaptations of the whole female body. In contrast, only a few is found about those adaptations in female prostate. Thus, this study aimed to evaluate the effect of estradiol and estradiol + testosterone association on gerbil female prostate in order to verify, which hormonal associations are necessary to its homeostasis. For this, adult females had the ovaries surgically removed. After recovering, they received estradiol and estradiol + testosterone doses through 30 days, each 48 h. The prostatic tissue underwent morphological and morphometric-estereological analysis. Hormonal restriction caused great gland involution and decreased secretory activity, aspects that were reverted by exposure to estradiol and estradiol + testosterone. However, these hormones were not able to re-establish the normal prostate histoarchitecture. The immunoreaction of steroid receptors (ER-α, ER-ß, and AR) responded differently among the experimental and control groups, and PCNA assay showed a decrease in epithelial cell proliferation within groups that had hormone privation. Therefore, we conclude that estradiol and testosterone are able to influence prostate morphophysiology and the maintenance of gland homeostasis depends on a balance among these and other hormones.
Assuntos
Androgênios/farmacologia , Estradiol/farmacologia , Estrogênios/farmacologia , Gerbillinae/anatomia & histologia , Próstata/efeitos dos fármacos , Testosterona/farmacologia , Animais , Feminino , Histocitoquímica , Humanos , Imuno-Histoquímica , Masculino , Próstata/anatomia & histologia , Próstata/citologiaRESUMO
AIMS: Little is known about the effect of progesterone on gerbil female prostate. It is known that normal oscillation in the progesterone and estradiol levels during the estrous cycle phases influence the morphophysiology of this gland. The present study aims to evaluate the isolated effect of prolonged administration of progesterone combined or not with testosterone on the prostate of ovariectomized female gerbil. MAIN METHODS: To observe the morphological changes caused by castration in the prostate of different groups stereologic analyses of all prostate compartments, analysis of nuclear area and perimeter, and morphometric measurements of epithelial and smooth muscle cells layers were used. In addition, immunocytochemistry was performed to investigate the distribution of the androgen, estrogen alfa and beta and progesterone receptors in different prostatic compartments. KEY FINDINGS: This study demonstrated that both treatments partially recovered the structure of the gland. In the group treated with progesterone plus testosterone a higher incidence of epithelial and stromal disorders occurred, besides the absence of secretory activity. Thus, treatment only with progesterone showed better results in the restoration of glandular homeostasis mainly seen by the regulation of the secretory activity. SIGNIFICANCE: Collectively, the findings of this study indicate that progesterone may have a significant role on the maintenance of prostate morphophysiology, and showed an interesting evidence of hormonal competition between progesterone and testosterone.