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.

FKBP52 deficiency–conferred uterine progesterone resistance is genetic background and pregnancy stage specific

“…Lactoferrin (Ltf) and complement factor 3 (C3) are induced to a high degree in the uterus by estrogen and antagonized by P 4 (28,29). They are abundantly expressed in the luminal epithelium on day 1 of pregnancy under the influence of a preovulatory estrogen surge but are dramatically downregulated on day 4 by rising P 4 levels from newly formed corpora lutea (1, 2).…”

Urinary Phytoestrogen Concentrations Are Not Associated with Incident Endometriosis in Premenopausal Women

“…Thus, it is not unexpected that dietary phytoestrogens could play a role in the pathophysiology of an estrogen-dependent (37) condition such as endometriosis. At the level of the endometrium, phytoestrogens have been shown to potentially act as agonists in animal models (38)(39)(40)(41). However, human studies have suggested that the dosage and length of supplementation may be important to consider because isoflavone treatment for a period of 5 y was associated with endometrial hyperplasia (19), whereas shortterm treatments were not (19,32,33).…”

17Beta-estradiol affects the response of complement components and survival of rainbow trout (Oncorhynchus mykiss) challenged by bacterial infection

“…Kuivanen et al (1989) also identified two estrogen-responsive proteins of the rat uterus as structurally related to complement component C3 [33]. Heikaus et al (2002) pointed to the supporting effect of estrogens on endometrial C3 gene expression [34]. Farkas et al (2008) found that neuroendocrine neurons of the rodent hypothalamus had significantly elevated complement C5a receptor transcriptions after estrogenic pretreatment and hypothesized that the C5a receptors are involved in the estrogen-induced calcium response of the hypothalamus, which links immune and neuroendocrine functions [35].…”