TY - JOUR
T1 - Involvement of androgen receptor in 17β-estradiol-induced cell proliferation in rat uterus
AU - Weihua, Zhang
AU - Ekman, Jenny
AU - Almkvist, Åsa
AU - Saji, Shigehira
AU - Wang, Ling
AU - Warner, Margaret
AU - Gustafsson, Jan Åke
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - Although it is known that, in the uterus, estrogen receptor α (ERα) is involved in proliferation and progesterone receptor in differentiation, the role of the two other gonadal-hormone receptors expressed in the uterus, androgen receptor (AR) and estrogen receptor β (ERβ), remains undefined. In this study, the involvement of AR in 17β-estradiol (E2)-induced cellular proliferation in the immature rat uterus was investigated. AR levels were low in the untreated immature uterus, but 24 h after treatment of rats with E2, there was an increase in the levels of AR and of two androgen-regulated genes, IGF-I and Crisp (cysteinerich secretory protein). As expected, E2 induced proliferation of luminal epithelial cells. These actions of E2 were all blocked by both the antiestrogen tamoxifen and the antiandrogen flutamide. The E2-induced AR was found by immunohistochemistry to be localized exclusively in the stroma, mainly in the myometrium, where it colocalized with ERα but not with ERβERβ, detected with two different ERβ-specific antibodies, was expressed in both stromal and epithelial cells either alone or together with ERα. Treatment with E2 caused down-regulation of ERα and ERβ in the epithelium. The data suggest that, in E2- induced epithelial cell proliferation, ERα induces stromal AR and AR amplifies the ERα signal by induction of IGF-I. Because AR is never expressed in cells with ERβ, it is unlikely that ERβ signaling is involved in this pathway. These results indicate an important role for AR in proliferation of the uterus, where estrogen and androgen do not represent separate pathways but are sequential steps in one pathway.
AB - Although it is known that, in the uterus, estrogen receptor α (ERα) is involved in proliferation and progesterone receptor in differentiation, the role of the two other gonadal-hormone receptors expressed in the uterus, androgen receptor (AR) and estrogen receptor β (ERβ), remains undefined. In this study, the involvement of AR in 17β-estradiol (E2)-induced cellular proliferation in the immature rat uterus was investigated. AR levels were low in the untreated immature uterus, but 24 h after treatment of rats with E2, there was an increase in the levels of AR and of two androgen-regulated genes, IGF-I and Crisp (cysteinerich secretory protein). As expected, E2 induced proliferation of luminal epithelial cells. These actions of E2 were all blocked by both the antiestrogen tamoxifen and the antiandrogen flutamide. The E2-induced AR was found by immunohistochemistry to be localized exclusively in the stroma, mainly in the myometrium, where it colocalized with ERα but not with ERβERβ, detected with two different ERβ-specific antibodies, was expressed in both stromal and epithelial cells either alone or together with ERα. Treatment with E2 caused down-regulation of ERα and ERβ in the epithelium. The data suggest that, in E2- induced epithelial cell proliferation, ERα induces stromal AR and AR amplifies the ERα signal by induction of IGF-I. Because AR is never expressed in cells with ERβ, it is unlikely that ERβ signaling is involved in this pathway. These results indicate an important role for AR in proliferation of the uterus, where estrogen and androgen do not represent separate pathways but are sequential steps in one pathway.
KW - Androgen receptor
KW - Estradiol receptor
KW - Female reproductive tract
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U2 - 10.1095/biolreprod67.2.616
DO - 10.1095/biolreprod67.2.616
M3 - Article
C2 - 12135905
AN - SCOPUS:0035992896
SN - 0006-3363
VL - 67
SP - 616
EP - 623
JO - Biology of Reproduction
JF - Biology of Reproduction
IS - 2
ER -