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Changes in Estrogen Receptor ERβ (ESR2) Expression without Changes in the Estradiol Levels in the Prostate of Aging Rats.

Morais-Santos M, Nunes AE, Oliveira AG, Moura-Cordeiro JD, Mahecha GA, Avellar MC, Oliveira CA - PLoS ONE (2015)

Bottom Line: Despite the relationship between reductions in ERβ and abnormal growth of the gland, little is known about the age-dependent variation of this receptor.The decrease in ERβ reactivity occurred in a hormonal milieu characterized by a constant concentration of estradiol and decreased plasmatic and tissue DHT.These data corroborate previous data from humans and dogs that silencing of this receptor may be associated with premalignant or malignant conditions in the prostate.

View Article: PubMed Central - PubMed

Affiliation: Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

ABSTRACT
Although the prostate is androgen-dependent, it is also influenced by estrogens, which act via the estrogen receptors ERα and ERβ. In the prostate, ERβ is highly expressed in the epithelium and appears to participate in the regulation of cell proliferation, apoptosis and differentiation. Evidence shows that ERβ is decreased in malignant prostate, suggesting that it plays an important role in protecting this tissue. Despite the relationship between reductions in ERβ and abnormal growth of the gland, little is known about the age-dependent variation of this receptor. Therefore, we aimed to investigate ERβ expression in the prostatic lobes of aging Wistar rats (3 to 24 months). Histopathological alterations, including hyperplasia, intraluminal concretions, nuclear atypia and prostate intraepithelial neoplasias (PIN), were observed in the prostates of aging rats. Epithelial proliferation led to cribriform architecture in some acini, especially in the ventral prostate (VP). In the VP, areas of epithelial atrophy were also observed. Furthermore, in the lateral prostate, there was frequent prostatitis. Immunohistochemistry revealed that the expression of ERβ is reduced in specific areas related to PIN, atrophic abnormalities and cellular atypia in the prostate epithelium of senile rats. Corroborating the involvement of the receptor with proliferative activity, the punctual reduction in ERβ paralleled the increase in cell proliferation especially in areas of PIN and nuclear atypies. The decrease in ERβ reactivity occurred in a hormonal milieu characterized by a constant concentration of estradiol and decreased plasmatic and tissue DHT. This paper is a pioneering study that reveals focal ERβ reduction in the prostate of aging rats and indicates a potential disorder in the ERβ pathway. These data corroborate previous data from humans and dogs that silencing of this receptor may be associated with premalignant or malignant conditions in the prostate.

No MeSH data available.


Related in: MedlinePlus

Colocalization of ERβ and the proliferation marker Ki67 in the ventral prostate of senile rats.(A) Comparison between normal epithelium (Ne), atrophic epithelium (Ae) and PIN areas. In PIN areas the ERβ immunoreaction is reduced especially in cells with nuclear atypies (PIN2), whereas the proliferating cells (arrowhead) were more frequently found. (B) 3D reconstruction of the areas demarcated in A. Inserts correspond to negative controls of the respective channels. Bar = 50 μm.
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pone.0131901.g007: Colocalization of ERβ and the proliferation marker Ki67 in the ventral prostate of senile rats.(A) Comparison between normal epithelium (Ne), atrophic epithelium (Ae) and PIN areas. In PIN areas the ERβ immunoreaction is reduced especially in cells with nuclear atypies (PIN2), whereas the proliferating cells (arrowhead) were more frequently found. (B) 3D reconstruction of the areas demarcated in A. Inserts correspond to negative controls of the respective channels. Bar = 50 μm.

Mentions: The fluorescence data corroborated the immunohistochemistry results. Few Ki67 positive cells were detected in normal epithelium, whereas in PIN areas the Ki67 positive cells were more frequently found. The ERβ fluorescence was constant in normal epithelium and reduced in atrophic epithelium (Fig 7A). In the PIN areas the ERβ fluorescence was heterogeneous with weakly reactive or unreactive nuclei found in the same area. The colocalization of ERβ and Ki67 revealed that the proliferating cells have low to undetectable positivity for ERβ, corroborating the antiproliferative profile of this receptor. Interestingly, in the PIN areas where nuclear atypies were predominant, most cells were unreactive for ERβ whereas the Ki67 positive cells were frequent (Fig 7B).


Changes in Estrogen Receptor ERβ (ESR2) Expression without Changes in the Estradiol Levels in the Prostate of Aging Rats.

Morais-Santos M, Nunes AE, Oliveira AG, Moura-Cordeiro JD, Mahecha GA, Avellar MC, Oliveira CA - PLoS ONE (2015)

Colocalization of ERβ and the proliferation marker Ki67 in the ventral prostate of senile rats.(A) Comparison between normal epithelium (Ne), atrophic epithelium (Ae) and PIN areas. In PIN areas the ERβ immunoreaction is reduced especially in cells with nuclear atypies (PIN2), whereas the proliferating cells (arrowhead) were more frequently found. (B) 3D reconstruction of the areas demarcated in A. Inserts correspond to negative controls of the respective channels. Bar = 50 μm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4492744&req=5

pone.0131901.g007: Colocalization of ERβ and the proliferation marker Ki67 in the ventral prostate of senile rats.(A) Comparison between normal epithelium (Ne), atrophic epithelium (Ae) and PIN areas. In PIN areas the ERβ immunoreaction is reduced especially in cells with nuclear atypies (PIN2), whereas the proliferating cells (arrowhead) were more frequently found. (B) 3D reconstruction of the areas demarcated in A. Inserts correspond to negative controls of the respective channels. Bar = 50 μm.
Mentions: The fluorescence data corroborated the immunohistochemistry results. Few Ki67 positive cells were detected in normal epithelium, whereas in PIN areas the Ki67 positive cells were more frequently found. The ERβ fluorescence was constant in normal epithelium and reduced in atrophic epithelium (Fig 7A). In the PIN areas the ERβ fluorescence was heterogeneous with weakly reactive or unreactive nuclei found in the same area. The colocalization of ERβ and Ki67 revealed that the proliferating cells have low to undetectable positivity for ERβ, corroborating the antiproliferative profile of this receptor. Interestingly, in the PIN areas where nuclear atypies were predominant, most cells were unreactive for ERβ whereas the Ki67 positive cells were frequent (Fig 7B).

Bottom Line: Despite the relationship between reductions in ERβ and abnormal growth of the gland, little is known about the age-dependent variation of this receptor.The decrease in ERβ reactivity occurred in a hormonal milieu characterized by a constant concentration of estradiol and decreased plasmatic and tissue DHT.These data corroborate previous data from humans and dogs that silencing of this receptor may be associated with premalignant or malignant conditions in the prostate.

View Article: PubMed Central - PubMed

Affiliation: Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

ABSTRACT
Although the prostate is androgen-dependent, it is also influenced by estrogens, which act via the estrogen receptors ERα and ERβ. In the prostate, ERβ is highly expressed in the epithelium and appears to participate in the regulation of cell proliferation, apoptosis and differentiation. Evidence shows that ERβ is decreased in malignant prostate, suggesting that it plays an important role in protecting this tissue. Despite the relationship between reductions in ERβ and abnormal growth of the gland, little is known about the age-dependent variation of this receptor. Therefore, we aimed to investigate ERβ expression in the prostatic lobes of aging Wistar rats (3 to 24 months). Histopathological alterations, including hyperplasia, intraluminal concretions, nuclear atypia and prostate intraepithelial neoplasias (PIN), were observed in the prostates of aging rats. Epithelial proliferation led to cribriform architecture in some acini, especially in the ventral prostate (VP). In the VP, areas of epithelial atrophy were also observed. Furthermore, in the lateral prostate, there was frequent prostatitis. Immunohistochemistry revealed that the expression of ERβ is reduced in specific areas related to PIN, atrophic abnormalities and cellular atypia in the prostate epithelium of senile rats. Corroborating the involvement of the receptor with proliferative activity, the punctual reduction in ERβ paralleled the increase in cell proliferation especially in areas of PIN and nuclear atypies. The decrease in ERβ reactivity occurred in a hormonal milieu characterized by a constant concentration of estradiol and decreased plasmatic and tissue DHT. This paper is a pioneering study that reveals focal ERβ reduction in the prostate of aging rats and indicates a potential disorder in the ERβ pathway. These data corroborate previous data from humans and dogs that silencing of this receptor may be associated with premalignant or malignant conditions in the prostate.

No MeSH data available.


Related in: MedlinePlus