Responsiveness of endometrial genes Connexin26, Connexin43, C3 and clusterin to primary estrogen, selective estrogen receptor modulators, phyto- and xenoestrogens

Abstract

Phytohormones and chemical compounds revealing estrogenic effects are of increasing interest for their possible influence on the physiology of the reproductive tract. The gap junction connexin (Cx) genes Cx26 and Cx43, the plasma glycoprotein clusterin gene and the complement C3 gene are highly regulated by estrogen in rat endometrium. To test the value of these genes as markers for estrogenic responsiveness we analyzed the effects of estradiol, diethylstilbestrol, the selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen, the phytoestrogens genistein and daidzein, and the industrial compounds DDT (1,1,1-trichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl) ethane) and polychlorinated biphenyl (PCB) on the transcription of these genes in rat endometrium in vivo. Enhancement of Cx26 and decrease of clusterin transcripts expression by estradiol was observed at 0·03 µg/250 g body weight (BW), and induction of C3 expression was observed at 0·05 µg/250 g BW. A comparable effect was obtained by a tenfold higher concentration of diethylstilbestrol. Tamoxifen had a regulatory effect on this set of genes at about a 300-fold higher concentration, while raloxifen revealed much weaker estrogenic activity. No effect on Cx43 transcripts was observed with any of the compounds at the concentrations used. An effect of genistein was observed only on Cx26 expression, while PCB decreased clusterin transcripts. These results show that Cx26, C3 and clusterin reveal a comparable sensitivity to estrogens and SERMs. With respect to the phytoestrogen genistein, however, Cx26 seems to be the most sensitive gene. The analysis of clusters of estrogen-sensitive endometrial genes could help to identify estrogenic substances, assess their potency, and elucidate their mechanism of action.

Gene expression responses in male fathead minnows exposed to binary mixtures of an estrogen and antiestrogen

“…There are no reports on whether or not this up-regulation is through an ERE in the promoter. Different from our results, clusterin (CLU) is down-regulated by E 2 in rat endometrium, but this regulation is reversed by tamoxifen, another ER antagonist [ 52 ]. CLU is known to be regulated by TGF beta and c-fos through an AP-1 site [ 53 ].…”

Gene expression responses in male fathead minnows exposed to binary mixtures of an estrogen and antiestrogen

“…There are no reports on whether or not this up-regulation is through an ERE in the promoter. Different from our results, clusterin (CLU) is down-regulated by E 2 in rat endometrium, but this regulation is reversed by tamoxifen, another ER antagonist [ 52 ]. CLU is known to be regulated by TGF beta and c-fos through an AP-1 site [ 53 ].…”

Estrogen-Responsive Gene Modulation by Mentha pulegium L. Extract in Uterine and Ovarian Tissues of Immature Rat

“…According to the transcriptional profiles of genes in the estradiol (E 2 ) and genes in MPE-treated, which demonstrate different levels of regulation, MPE may have substantially lower estrogenic efficacy than estradiol. As expected, administering E 2 to the E 2 -treated group produced the most sensitive gene expression regulation, also observed in a study by [37]. Estradiol binds to the ER and causes a displacement of some chaperone proteins.…”

Genistein Suppresses Spontaneous Oviduct Tumorigenesis in Quail

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Gene expression responses in male fathead minnows exposed to binary mixtures of an estrogen and antiestrogen

“…There are no reports on whether or not this up-regulation is through an ERE in the promoter. Different from our results, clusterin (CLU) is down-regulated by E 2 in rat endometrium, but this regulation is reversed by tamoxifen, another ER antagonist [ 52 ]. CLU is known to be regulated by TGF beta and c-fos through an AP-1 site [ 53 ].…”

Estrogen-Responsive Gene Modulation by Mentha pulegium L. Extract in Uterine and Ovarian Tissues of Immature Rat

“…According to the transcriptional profiles of genes in the estradiol (E 2 ) and genes in MPE-treated, which demonstrate different levels of regulation, MPE may have substantially lower estrogenic efficacy than estradiol. As expected, administering E 2 to the E 2 -treated group produced the most sensitive gene expression regulation, also observed in a study by [37]. Estradiol binds to the ER and causes a displacement of some chaperone proteins.…”

Genistein Suppresses Spontaneous Oviduct Tumorigenesis in Quail

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“……”

Gene expression responses in male fathead minnows exposed to binary mixtures of an estrogen and antiestrogen

“…There are no reports on whether or not this up-regulation is through an ERE in the promoter. Different from our results, clusterin (CLU) is down-regulated by E 2 in rat endometrium, but this regulation is reversed by tamoxifen, another ER antagonist [ 52 ]. CLU is known to be regulated by TGF beta and c-fos through an AP-1 site [ 53 ].…”

Estrogen-Responsive Gene Modulation by Mentha pulegium L. Extract in Uterine and Ovarian Tissues of Immature Rat

“…According to the transcriptional profiles of genes in the estradiol (E 2 ) and genes in MPE-treated, which demonstrate different levels of regulation, MPE may have substantially lower estrogenic efficacy than estradiol. As expected, administering E 2 to the E 2 -treated group produced the most sensitive gene expression regulation, also observed in a study by [37]. Estradiol binds to the ER and causes a displacement of some chaperone proteins.…”

Genistein Suppresses Spontaneous Oviduct Tumorigenesis in Quail

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