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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

Quantification of ERβ immunoreactivity in the ventral and dorsal prostates of rats at different ages.(A–B) Compared to the normal adjacent epithelium, the areas of hyperplasia were similarly stained for ERβ, whereas those of PIN (C–D) and atrophy (E) showed decreased ERβ immunoreactivity. * = p ≤ 0.05; n = 4 per group.
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pone.0131901.g003: Quantification of ERβ immunoreactivity in the ventral and dorsal prostates of rats at different ages.(A–B) Compared to the normal adjacent epithelium, the areas of hyperplasia were similarly stained for ERβ, whereas those of PIN (C–D) and atrophy (E) showed decreased ERβ immunoreactivity. * = p ≤ 0.05; n = 4 per group.

Mentions: The pattern and intensity of ERβ immunoreactivity did not change with age, when considering the epithelium of acini with normal morphology or those with hyperplasia (Figs 2B and 2H and 3A and 3B). On the other hand, the ERβ reaction was significantly reduced in areas of intraepithelial neoplasia, especially in those PIN where cellular atypies were predominant (Fig 3C and 3D). In these focal areas, a heterogeneous pattern of staining as weakly stained or unstained cells was observed along with cells positive for the receptor (Fig 2C, 2D, 2I and 2J). In the ventral prostate, the atrophic epithelium was also weakly stained (Figs 2F and 3E). Accordingly, in areas of change from normal to squamous epithelium, ERβ staining intensity gradually reduced (Fig 2F).


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)

Quantification of ERβ immunoreactivity in the ventral and dorsal prostates of rats at different ages.(A–B) Compared to the normal adjacent epithelium, the areas of hyperplasia were similarly stained for ERβ, whereas those of PIN (C–D) and atrophy (E) showed decreased ERβ immunoreactivity. * = p ≤ 0.05; n = 4 per group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131901.g003: Quantification of ERβ immunoreactivity in the ventral and dorsal prostates of rats at different ages.(A–B) Compared to the normal adjacent epithelium, the areas of hyperplasia were similarly stained for ERβ, whereas those of PIN (C–D) and atrophy (E) showed decreased ERβ immunoreactivity. * = p ≤ 0.05; n = 4 per group.
Mentions: The pattern and intensity of ERβ immunoreactivity did not change with age, when considering the epithelium of acini with normal morphology or those with hyperplasia (Figs 2B and 2H and 3A and 3B). On the other hand, the ERβ reaction was significantly reduced in areas of intraepithelial neoplasia, especially in those PIN where cellular atypies were predominant (Fig 3C and 3D). In these focal areas, a heterogeneous pattern of staining as weakly stained or unstained cells was observed along with cells positive for the receptor (Fig 2C, 2D, 2I and 2J). In the ventral prostate, the atrophic epithelium was also weakly stained (Figs 2F and 3E). Accordingly, in areas of change from normal to squamous epithelium, ERβ staining intensity gradually reduced (Fig 2F).

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