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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

Immunostaining for ERβ is affected in specific areas of alterations related to aging.(A–F) Immunostaining for ERβ in the ventral and (G–K) dorsal prostate of rats at different ages. (A and G) Young adult animals showing intense positivity for the receptor in the epithelial luminal (l) and basal cells (b). Black arrowhead = positive perialveolar smooth muscle cells. (B and H) Senile rats presenting unfolding of the epithelium with normal ERβ expression. (C–D and I–J) Areas of intraepithelial proliferation (*) in the ventral and dorsal prostate, respectively, showing reduced ERβ staining compared with the normal epithelium (Ne). Insert in C and I: immunostaining for CK HMW in the ventral (C) and dorsal (I) prostate showing that the dorsal prostate presents a greater number of basal cells in intraepithelial proliferating areas. (E and K) Drastic reduction of ERβ immunostaining in areas of intense cellular atypia. (F) Transition from normal epithelium (Ne) showing standard ERβ positivity to atrophic epithelium (Ae) presenting a marked decrease in receptor staining. (L and M) Negative immunostaining controls for the ventral and dorsal prostate, respectively. Lu: lumen. Bar in A and G (= B, C, E, F, H, I, J, K) = 50 μm; bar in D = 40 μm; bar in M (= L) = 30 μm.
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pone.0131901.g002: Immunostaining for ERβ is affected in specific areas of alterations related to aging.(A–F) Immunostaining for ERβ in the ventral and (G–K) dorsal prostate of rats at different ages. (A and G) Young adult animals showing intense positivity for the receptor in the epithelial luminal (l) and basal cells (b). Black arrowhead = positive perialveolar smooth muscle cells. (B and H) Senile rats presenting unfolding of the epithelium with normal ERβ expression. (C–D and I–J) Areas of intraepithelial proliferation (*) in the ventral and dorsal prostate, respectively, showing reduced ERβ staining compared with the normal epithelium (Ne). Insert in C and I: immunostaining for CK HMW in the ventral (C) and dorsal (I) prostate showing that the dorsal prostate presents a greater number of basal cells in intraepithelial proliferating areas. (E and K) Drastic reduction of ERβ immunostaining in areas of intense cellular atypia. (F) Transition from normal epithelium (Ne) showing standard ERβ positivity to atrophic epithelium (Ae) presenting a marked decrease in receptor staining. (L and M) Negative immunostaining controls for the ventral and dorsal prostate, respectively. Lu: lumen. Bar in A and G (= B, C, E, F, H, I, J, K) = 50 μm; bar in D = 40 μm; bar in M (= L) = 30 μm.

Mentions: In the ventral, dorsal and lateral prostate, areas of intraepithelial stratification occurred, with preserved basement membrane and often with atypical cells, which were compatible with prostate intraepithelial neoplasias (PIN) (Fig 1F, 1G, 1J, 1O, 1S and insert in 1N). In the dorsal lobe, the proliferation was primarily in the basal compartment (Fig 1J). The identity of these cells as basal cells was confirmed according to CK HMW positivity (insert in Fig 2I).


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)

Immunostaining for ERβ is affected in specific areas of alterations related to aging.(A–F) Immunostaining for ERβ in the ventral and (G–K) dorsal prostate of rats at different ages. (A and G) Young adult animals showing intense positivity for the receptor in the epithelial luminal (l) and basal cells (b). Black arrowhead = positive perialveolar smooth muscle cells. (B and H) Senile rats presenting unfolding of the epithelium with normal ERβ expression. (C–D and I–J) Areas of intraepithelial proliferation (*) in the ventral and dorsal prostate, respectively, showing reduced ERβ staining compared with the normal epithelium (Ne). Insert in C and I: immunostaining for CK HMW in the ventral (C) and dorsal (I) prostate showing that the dorsal prostate presents a greater number of basal cells in intraepithelial proliferating areas. (E and K) Drastic reduction of ERβ immunostaining in areas of intense cellular atypia. (F) Transition from normal epithelium (Ne) showing standard ERβ positivity to atrophic epithelium (Ae) presenting a marked decrease in receptor staining. (L and M) Negative immunostaining controls for the ventral and dorsal prostate, respectively. Lu: lumen. Bar in A and G (= B, C, E, F, H, I, J, K) = 50 μm; bar in D = 40 μm; bar in M (= L) = 30 μm.
© Copyright Policy
Related In: Results  -  Collection

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pone.0131901.g002: Immunostaining for ERβ is affected in specific areas of alterations related to aging.(A–F) Immunostaining for ERβ in the ventral and (G–K) dorsal prostate of rats at different ages. (A and G) Young adult animals showing intense positivity for the receptor in the epithelial luminal (l) and basal cells (b). Black arrowhead = positive perialveolar smooth muscle cells. (B and H) Senile rats presenting unfolding of the epithelium with normal ERβ expression. (C–D and I–J) Areas of intraepithelial proliferation (*) in the ventral and dorsal prostate, respectively, showing reduced ERβ staining compared with the normal epithelium (Ne). Insert in C and I: immunostaining for CK HMW in the ventral (C) and dorsal (I) prostate showing that the dorsal prostate presents a greater number of basal cells in intraepithelial proliferating areas. (E and K) Drastic reduction of ERβ immunostaining in areas of intense cellular atypia. (F) Transition from normal epithelium (Ne) showing standard ERβ positivity to atrophic epithelium (Ae) presenting a marked decrease in receptor staining. (L and M) Negative immunostaining controls for the ventral and dorsal prostate, respectively. Lu: lumen. Bar in A and G (= B, C, E, F, H, I, J, K) = 50 μm; bar in D = 40 μm; bar in M (= L) = 30 μm.
Mentions: In the ventral, dorsal and lateral prostate, areas of intraepithelial stratification occurred, with preserved basement membrane and often with atypical cells, which were compatible with prostate intraepithelial neoplasias (PIN) (Fig 1F, 1G, 1J, 1O, 1S and insert in 1N). In the dorsal lobe, the proliferation was primarily in the basal compartment (Fig 1J). The identity of these cells as basal cells was confirmed according to CK HMW positivity (insert in Fig 2I).

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