Antiproliferative and apoptotic effect of epigallocatechin-3-gallate on Ishikawa cells is accompanied by sex steroid receptor downregulation

Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of colitis. We utilized a dextran sodium sulfate (DSS)-induced colitis model in FVB/n mice to demonstrate the effects of orally administered SERM2 on the clinical status of the mice and the histopathological changes in the colon, as well as proportion of Mrc-1 positive macrophages. SERM2 nuclear receptor affinities were measured by radioligand binding assays. Orally administered, this compound significantly alleviated DSS-induced colitis in male mice and induced local estrogen receptor activation in the inflamed colon, as well as promoting anti-inflammatory cytokine expression and infiltration of anti-inflammatory monocytes. We show that this novel drug candidate has an affinity to estrogen receptors α and β and progesterone receptors, but not to glucocorticoid receptor, thus expressing unique binding properties compared to other sex steroid receptor ligands. These results indicate that novel drug candidates to alleviate inflammatory conditions of the colon could be found among sex steroid receptor activating compounds.

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Comparison of sex steroid receptor determinations in human breast cancer by enzyme immunoassay and radioligand binding

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.1860040608 ◽

1990 ◽

Vol 4 (6) ◽

pp. 430-436 ◽

Cited By ~ 21

Author(s):

Resad Pasic ◽

Benjamin Djulbegovic ◽

James L. Wittliff

Keyword(s):

Breast Cancer ◽

Enzyme Immunoassay ◽

Human Breast Cancer ◽

Radioligand Binding ◽

Steroid Receptor ◽

Sex Steroid ◽

Human Breast

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Regulation of the androgen receptor in human genital skin fibroblasts, with a review of sex steroid receptor regulation by homologous and heterologous steroids

Canadian Journal of Biochemistry and Cell Biology ◽

10.1139/o83-097 ◽

1983 ◽

Vol 61 (7) ◽

pp. 770-778 ◽

Cited By ~ 15

Author(s):

Leonard Pinsky ◽

Morris Kaufman ◽

Carmen Gil-Esteban ◽

Datevik Sumbulian

Keyword(s):

Androgen Receptor ◽

Calf Serum ◽

Steroid Receptor ◽

Skin Fibroblasts ◽

Sex Steroid ◽

Receptor Regulation ◽

Time Pattern ◽

Regulatory Behavior ◽

Androgen Receptor Activity ◽

Interexperimental Variation

When normal human genital skin fibroblasts are cultured for 3 days with 2–3 nM methyltrienolone (R1881, a synthetic nonmetabolizable androgen), they augment their specific androgen-receptor activity (two- to four-fold) with a time pattern that is always most rapid in the first 24 h, usually peaks by 48 h, and often declines, sometimes substantially, in the third 24-h interval. The time pattern is highly reproducible within experiments on confluent monolayers and is not influenced by the presence or absence of 10% fetal calf serum in the medium, the temperature (37 vs. 40 °C) at which the incubation is conducted, or the basal activity (up to 40 fmol/mg protein) that is saturated by incubation for 30–45 min at 37 °C. It does appear to be influenced by an unusually rapid increase in the first 24 h and by nonconfluent density of the monolayers, but these factors do not explain the considerable interexperimental variation, within and among cell lines, under nominally identical conditions. The time pattern is interpreted to represent an initial phase of "up-regulation" that is followed by one of compensatory adjustment, despite a constant level of unmetabolized ligand. A review of sex steroid receptor regulation by homologous and heterologous sex steroids reveals numerous examples of apparently homologous regulatory behavior.

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