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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

Histopathology of the prostatic complex of rats at different ages.Ventral (A-G); dorsal (H-K); lateral (L-O) and anterior (P-S) prostate. (A, H, L and P) Prostates of young adult rats showed normal histology. (B, I, M and Q) Senile rats showed increased unfolding of the epithelium (arrows) in all prostatic lobes. (B) Luminal concretions (c). (C) Epithelial proliferation resulted in cribriform architecture with intraluminal growing (*) in the ventral prostate. (D) Mucinous metaplasia of the epithelium (bounded area). (E) Epithelial atrophy (a) and area of a cell with nuclear enlargement and prominence of nucleoli (n). (F and G) Hyperproliferative epithelium with characteristic foci of prostatic intraepithelial neoplasia (PIN). (G) Cells with evident nuclear enlargement (n) in the PIN area. (J) Detail of the prostatic intraepithelial proliferation observed in the bounded area of the dorsal prostate in panel I. (K) Epithelial proliferation with papillary growth. Thickening of the stroma (**) occurred around the lesion. (N) Lateral prostate with epithelial hyperplasia (arrow) as well as foci of inflammatory cells infiltrating the epithelium (bounded area), lumen (#) and stroma (i). (O) PIN area next to an inflammatory cell infiltrate containing plasma cells (Pl). Cells sloughed into the lumen (sc). (R) Intense unfolding and vacuolization in the epithelium of the anterior prostate (v). (S) PIN area in the anterior prostate with some nuclear atypia (n). Arrowhead = perialveolar smooth muscle cell; Pl = plasma cells; bv = blood vessel; c = luminal concretions; Lu = lumen. Stained with H&E.
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pone.0131901.g001: Histopathology of the prostatic complex of rats at different ages.Ventral (A-G); dorsal (H-K); lateral (L-O) and anterior (P-S) prostate. (A, H, L and P) Prostates of young adult rats showed normal histology. (B, I, M and Q) Senile rats showed increased unfolding of the epithelium (arrows) in all prostatic lobes. (B) Luminal concretions (c). (C) Epithelial proliferation resulted in cribriform architecture with intraluminal growing (*) in the ventral prostate. (D) Mucinous metaplasia of the epithelium (bounded area). (E) Epithelial atrophy (a) and area of a cell with nuclear enlargement and prominence of nucleoli (n). (F and G) Hyperproliferative epithelium with characteristic foci of prostatic intraepithelial neoplasia (PIN). (G) Cells with evident nuclear enlargement (n) in the PIN area. (J) Detail of the prostatic intraepithelial proliferation observed in the bounded area of the dorsal prostate in panel I. (K) Epithelial proliferation with papillary growth. Thickening of the stroma (**) occurred around the lesion. (N) Lateral prostate with epithelial hyperplasia (arrow) as well as foci of inflammatory cells infiltrating the epithelium (bounded area), lumen (#) and stroma (i). (O) PIN area next to an inflammatory cell infiltrate containing plasma cells (Pl). Cells sloughed into the lumen (sc). (R) Intense unfolding and vacuolization in the epithelium of the anterior prostate (v). (S) PIN area in the anterior prostate with some nuclear atypia (n). Arrowhead = perialveolar smooth muscle cell; Pl = plasma cells; bv = blood vessel; c = luminal concretions; Lu = lumen. Stained with H&E.

Mentions: Compared to adult animals at three to six month of age, morphological alterations were observed in all prostatic lobes from 12 to 24 months (Fig 1). The changes were heterogeneous among animals of the same age and even within the glands of the same animal, in which normal acini colocalized with altered ones. The initial changes included slight to moderate unfolding of the acinar epithelium, which is suggestive of hyperplasia. Intraluminal concretions and cellular atypia, such as cytoplasmic vacuolization, as well as nuclear enlargement and the prominence of nucleoli were also observed (Fig 1). From 18 to 24 months of age, the prostatic concretions and the areas of hyperplasia and cellular atypia were more frequently observed and pronounced than those observed at 12 months of age (Fig 1B, 1I, 1M and 1Q), except for the anterior prostate in which the concretion contents did not vary with age. Proliferation of the epithelium led to cribriform or papillary architecture in some acini, especially in the ventral prostate (Fig 1C).


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)

Histopathology of the prostatic complex of rats at different ages.Ventral (A-G); dorsal (H-K); lateral (L-O) and anterior (P-S) prostate. (A, H, L and P) Prostates of young adult rats showed normal histology. (B, I, M and Q) Senile rats showed increased unfolding of the epithelium (arrows) in all prostatic lobes. (B) Luminal concretions (c). (C) Epithelial proliferation resulted in cribriform architecture with intraluminal growing (*) in the ventral prostate. (D) Mucinous metaplasia of the epithelium (bounded area). (E) Epithelial atrophy (a) and area of a cell with nuclear enlargement and prominence of nucleoli (n). (F and G) Hyperproliferative epithelium with characteristic foci of prostatic intraepithelial neoplasia (PIN). (G) Cells with evident nuclear enlargement (n) in the PIN area. (J) Detail of the prostatic intraepithelial proliferation observed in the bounded area of the dorsal prostate in panel I. (K) Epithelial proliferation with papillary growth. Thickening of the stroma (**) occurred around the lesion. (N) Lateral prostate with epithelial hyperplasia (arrow) as well as foci of inflammatory cells infiltrating the epithelium (bounded area), lumen (#) and stroma (i). (O) PIN area next to an inflammatory cell infiltrate containing plasma cells (Pl). Cells sloughed into the lumen (sc). (R) Intense unfolding and vacuolization in the epithelium of the anterior prostate (v). (S) PIN area in the anterior prostate with some nuclear atypia (n). Arrowhead = perialveolar smooth muscle cell; Pl = plasma cells; bv = blood vessel; c = luminal concretions; Lu = lumen. Stained with H&E.
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Related In: Results  -  Collection

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pone.0131901.g001: Histopathology of the prostatic complex of rats at different ages.Ventral (A-G); dorsal (H-K); lateral (L-O) and anterior (P-S) prostate. (A, H, L and P) Prostates of young adult rats showed normal histology. (B, I, M and Q) Senile rats showed increased unfolding of the epithelium (arrows) in all prostatic lobes. (B) Luminal concretions (c). (C) Epithelial proliferation resulted in cribriform architecture with intraluminal growing (*) in the ventral prostate. (D) Mucinous metaplasia of the epithelium (bounded area). (E) Epithelial atrophy (a) and area of a cell with nuclear enlargement and prominence of nucleoli (n). (F and G) Hyperproliferative epithelium with characteristic foci of prostatic intraepithelial neoplasia (PIN). (G) Cells with evident nuclear enlargement (n) in the PIN area. (J) Detail of the prostatic intraepithelial proliferation observed in the bounded area of the dorsal prostate in panel I. (K) Epithelial proliferation with papillary growth. Thickening of the stroma (**) occurred around the lesion. (N) Lateral prostate with epithelial hyperplasia (arrow) as well as foci of inflammatory cells infiltrating the epithelium (bounded area), lumen (#) and stroma (i). (O) PIN area next to an inflammatory cell infiltrate containing plasma cells (Pl). Cells sloughed into the lumen (sc). (R) Intense unfolding and vacuolization in the epithelium of the anterior prostate (v). (S) PIN area in the anterior prostate with some nuclear atypia (n). Arrowhead = perialveolar smooth muscle cell; Pl = plasma cells; bv = blood vessel; c = luminal concretions; Lu = lumen. Stained with H&E.
Mentions: Compared to adult animals at three to six month of age, morphological alterations were observed in all prostatic lobes from 12 to 24 months (Fig 1). The changes were heterogeneous among animals of the same age and even within the glands of the same animal, in which normal acini colocalized with altered ones. The initial changes included slight to moderate unfolding of the acinar epithelium, which is suggestive of hyperplasia. Intraluminal concretions and cellular atypia, such as cytoplasmic vacuolization, as well as nuclear enlargement and the prominence of nucleoli were also observed (Fig 1). From 18 to 24 months of age, the prostatic concretions and the areas of hyperplasia and cellular atypia were more frequently observed and pronounced than those observed at 12 months of age (Fig 1B, 1I, 1M and 1Q), except for the anterior prostate in which the concretion contents did not vary with age. Proliferation of the epithelium led to cribriform or papillary architecture in some acini, especially in the ventral prostate (Fig 1C).

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