Molecular mechanism of estrogen receptor (ER)α-specific, estradiol-dependent expression of the progesterone receptor (PR) B-isoform

Flötotto, T; Niederacher, Dieter; Hohmann, Dagmar; Heimerzheim, T.; Dall, P.; Djahansouzi, S.; Bender, H. G.; Hanstein, Bettina

doi:10.1016/j.jsbmb.2003.11.004

Cited by 37 publications

(26 citation statements)

References 35 publications

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“…In the ER-a-knockout mouse, expression of both uterine PR-A and PR-B was reduced to 60% of normal levels, but estrogen treatment did not restore their expression under a presumably intact ER-b axis (Hewitt and Korach, 2000). In HeLa, BT20, and Ishikawa cell lines, PR-B promoter activity was enhanced by ER-a, but not by ER-b, while in SK-BR-3 cells both ER subtypes repressed PR-B promoter activity (Flototto et al, 2004). In osteoblasts, although both ER subtypes enhanced PR-B promoter activity, activation of the PR-A promoter clearly showed a preferential dependency on ER-a (Rickard et al, 2002).…”

Section: Discussionmentioning

confidence: 89%

Estrogen-induced loss of progesterone receptor expression in normal and malignant ovarian surface epithelial cells

Mukherjee

Syed

2005

Oncogene

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Section: Discussionmentioning

confidence: 89%

Estrogen-induced loss of progesterone receptor expression in normal and malignant ovarian surface epithelial cells

Mukherjee

Syed

2005

Oncogene

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“…Thus, progesterone and 17␤-estradiol could affect each other in regulation of BCRP, when the two hormones are combined. The real situation could be very complex, because 17␤-estradiol can induce PRB expression (Flötotto et al, 2004;Wang et al, 2006) and down-regulate BCRP expression through posttranscriptional modification (Imai et al, 2005); on the other hand, PRA can repress the estrogen receptor activity (Giangrande and McDonnell, 1999). In BeWo cells, we showed previously that the 17␤-estradiol treatment alone down-regulated BCRP expression , presumably as a result of post-transcriptional modification, as demonstrated by Imai et al (2005); however, the combined treatment of BeWo cells with 17␤-estradiol and progesterone significantly increased BCRP expression compared with progesterone treatment alone .…”

Section: Differential Regulation Of Bcrp Via Progesterone Receptors 851mentioning

confidence: 99%

Progesterone Receptor (PR) Isoforms PRA and PRB Differentially Regulate Expression of the Breast Cancer Resistance Protein in Human Placental Choriocarcinoma BeWo Cells

et al. 2007

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Breast cancer resistance protein (BCRP) plays a significant role in drug disposition and in conferring multidrug resistance in cancer cells. Previous studies have shown that steroid hormones such as 17␤-estradiol and progesterone can affect BCRP expression in cancer cells. In this study, we investigated the molecular mechanism by which BCRP expression in human placental choriocarcinoma BeWo cells is regulated by progesterone. Transfection of the progesterone receptor (PR) isoforms PRA and PRB resulted in a similarly increased expression of PRA and PRB, respectively. However, progesterone significantly increased BCRP expression and activity only in PRBtransfected cells. This stimulatory effect of progesterone was abrogated by the PR antagonist mifepristone (RU-486). Consistently, transcriptional activity of the BCRP promoter was induced 2-to 6-fold by 10 Ϫ8 to 10 Ϫ5 M progesterone in PRBtransfected cells. Progesterone had little effect on BCRP expression and activity and transcriptional activity of the BCRP promoter in PRA-transfected cells; however, cotransfection of PRA and PRB significantly decreased the progesterone-response compared with that in cells transfected with only PRB. Mutations in a novel progesterone response element (PRE) identified between Ϫ243 to Ϫ115 bp of the BCRP promoter region significantly attenuated the progesterone-response in PRB-transfected cells, and deletion of the PRE nearly completely abrogated the progesterone effect. Specific binding of both PRA and PRB to the BCRP promoter through the identified PRE was confirmed using the electrophoretic mobility shift assay. Collectively, progesterone induces BCRP expression in BeWo cells via PRB but not PRA. PRA represses the PRB activity. Thus, PRA and PRB differentially regulate BCRP expression in BeWo cells.

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“…PR A and PR B expression are controlled by two different promoters that are both estrogenregulated [41] and consistent with this notion, uterine PR A increased following both regimens whereas only constant estrogen was sufficient to increase PR B . PR B expression can be stimulated via ERa, but not ERb [42]; although, it is unclear why PR B levels were higher in constant estrogentreated rats who had reduced levels of uterine ERa. PR A can repress PR B [43], which functions as a more potent activator of transcription of PR target genes [44].…”

Section: Discussionmentioning

confidence: 99%

Estrogen replacement regimen and brain infusion of lipopolysaccharide differentially alter steroid receptor expression in the uterus and hypothalamus

Marriott

McGann-Gramling

Hauss–Wegrzyniak

et al. 2007

Endocr

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The regimen of estrogen replacement can alter the consequences of estrogen therapy and stressors. To determine the long-term effects and interaction of these systems on the brain and periphery, adult female rats were infused with lipopolysaccharide (LPS) into the fourth ventricle of the brain for 4 weeks, and ovariectomized rats were administered either constant or pulsed regimens of estrogen replacement (17beta-estradiol) until sacrifice at 8 weeks. Constant, but not pulsed, estrogen replacement reduced ERalpha and increased HSP90, HSP70, and PR(B) uterine protein levels. Both estrogen regimens increased ERbeta, HSP27, and PR(A) uterine proteins. Both regimens reduced hypothalamic levels of ERalpha, but not ERbeta, HSP, or PR. No changes were observed in the hippocampus. Long-term brain infusion of LPS activated microglia and reduced body weight, but did not alter corticosterone or nitrotyrosine levels. LPS infusion into intact rats suppressed uterine weight, increased ERalpha and decreased HSP90 in the uterus. LPS did not alter uterine weight in ovariectomized rats treated with constant or pulsed estrogen. Together, these data suggest the timing of estrogen replacement and neuroinflammatory stressors can profoundly affect uterine and hypothalamic steroid receptor expression and may be important parameters to consider in the post-menopausal intervention with estrogen.

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Molecular mechanism of estrogen receptor (ER)α-specific, estradiol-dependent expression of the progesterone receptor (PR) B-isoform

Cited by 37 publications

References 35 publications

Estrogen-induced loss of progesterone receptor expression in normal and malignant ovarian surface epithelial cells

Estrogen-induced loss of progesterone receptor expression in normal and malignant ovarian surface epithelial cells

Progesterone Receptor (PR) Isoforms PRA and PRB Differentially Regulate Expression of the Breast Cancer Resistance Protein in Human Placental Choriocarcinoma BeWo Cells

Estrogen replacement regimen and brain infusion of lipopolysaccharide differentially alter steroid receptor expression in the uterus and hypothalamus

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