Effect of Oestradiol on Cell Proliferation and Histological Changes in the Uterus and Vagina of Mice

Galand, Paul; Leroy, Fernand; Chrétien, Jean-Pierre

doi:10.1677/joe.0.0490243

Cited by 104 publications

(56 citation statements)

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“…In a preliminary study, we also found that BPA induced expression of c-jun in both strains of rats, with steadystate levels reaching maximum at 2-3 hr after treatment (data not shown). Likewise, the time-course of the DNA synthetic response in the F344 vagina following a single injection of BPA is similar to that produced by natural estrogens (26,27). In studies on estrogenic effects in non-reproductive tissues, Dodge et al (25) (2).…”

Section: Resultsmentioning

confidence: 92%

Strain differences in vaginal responses to the xenoestrogen bisphenol A.

Long

Steinmetz

Ben‐Jonathan

et al. 2000

Environ Health Perspect

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Bisphenol A (BPA) is the monomer component of polycarbonate plastics and epoxy resins; human exposure derives from leachate in foodstuffs packaged in certain plastics or from epoxybased dental appliances. BPA (6). Although it is almost entirely in its polymerized form, the BPA monomer finds its way into foodstuffs as a leachate of plastic packaging (7,8). Also, humans can be exposed to BPA from certain dental appliances (9,10). Because of its estrogenic activity, there is concern over human exposure to BPA.When assessing the biologic activity of a putative estrogenic compound in animal model systems, it is important to consider species and strain differences. We previously found that BPA increased blood prolactin levels in Fischer 344 (F344) but not SpragueDawley (S-D) rats (3). Such a finding is congruent with the earlier observation that estrogens stimulate growth of the pituitary through replication of the prolactin-secreting cells in F344 rats but not in outbred rat strains (11-13). We also found that the uterine epithelium of F344 rats but not that of S-D rats exhibited a hypertrophic response to BPA administered in low doses (2 (15)(16)(17)(18). The induction of these genes is believed to play a key role in cell proliferation (19,20). In the present study, we determined the potency of BPA to induce immediate early gene expression and DNA synthetic activity in the vaginal epithelium of F344 and S-D rats. Materials and MethodsAnimals. All procedures performed on animals followed the NIH Guide for the Care and Use ofLaboratory Animals (21) and were approved by the Indiana University Animal Care and Use Committee. F344 and S-D rats were supplied at 6-8 weeks of age by Harlan Sprague-Dawley (Indianapolis, IN). One week after arrival, animals were ovariectomized under ketamine anesthesia; they were subjected to experimental manipulation 3 weeks later. BPA (Aldrich Chemical Co., Milwaukee, WI) and 17,B-estradiol (E2; Sigma Chemical Company, St. Louis, MO) were dissolved in ethanol and diluted in sesame oil. Compounds were injected intraperitoneally (ip) in 50 pL of solution. We injected BPA at 0.2-150 mg/kg body weight (bw) and E2 at 0.02-2.0 pg/kg bw.Bromodeoxyuridine immunostaining. Animals were injected with bromodeoxyuridine (BrdU; 100 mg/kg bw in 500 pL saline, ip) and killed 1 hr later. Tissue taken from treated animals was fixed in ethanol-chloroform-acetic acid (60:30:10, vol/vol/vol)

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Section: Resultsmentioning

confidence: 92%

Strain differences in vaginal responses to the xenoestrogen bisphenol A.

Long

Steinmetz

Ben‐Jonathan

et al. 2000

Environ Health Perspect

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“…Oestrogen is known to regulate diverse physiological processes of target tissues including those of the reproductive (Galand et al 1971), cardiovascular (Barrett-Connor & Bush 1991) and skeletal (Migliaccio et al 1992) systems. These tissues have been shown to express oestrogenbinding molecules, namely oestrogen receptors (ER), by studies using various techniques such as binding assays (Eisenfeld 1970, Saiduddin & Milor 1971, Sen & Talwar 1973, autoradiography (Stumpf & Sar 1975), immunohistochemistry (Greene et al 1984), reverse transcriptasepolymerase chain reaction (RT-PCR) (Couse et al 1997 and in situ hybridization (Kuiper et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Differential distribution of oestrogen receptor-alpha and -beta mRNAs in the female reproductive organ of rats as revealed by in situ hybridization

Mowa

Iwanaga²

2000

Journal of Endocrinology

101

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The cellular distribution of two oestrogen receptor (ER) subtypes, ER and ER mRNAs, was studied in the entire female reproductive organ of the rat using in situ hybridization. Expression of ER and ER mRNAs was predominant in the reproductive tract and ovary respectively. ER mRNA had the most pronounced expression in epithelial cells and subepithelial stromal cells from the oviduct to the vagina, while in the ovary it was moderately detected in only the theca folliculi and interstitial glands. The oviduct showed a region-dependent expression of ER mRNA: the isthmus had the most intense signals while the infundibulum revealed a low intensity of expression. Signals for ER mRNA in the ovary were most intense in the granulosa cells of healthy follicles, whereas degenerating follicles lacked any significant expression. Less intense signals for ER mRNA were localized in the theca folliculi and corpus luteum. Detectable levels of ER mRNA were observed in the subepithelial stromal cells from the oviduct to the vagina. This study shows that the two ER subtypes are differentially expressed in cells and compartments of the reproductive organ, suggesting that the mediation of oestrogen action in these tissues may be accomplished through the respective predominant receptor.

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“…Significant increases of uterine weight and endometrial height, as well as hypertrophy of the luminal epihelium, have been established as reliable indexes of estrogenic effects (Galand et al, 1971;Korach and McLachlan, 1995;Tinwell et al, 2000). The most pronounced uterotrophic effects were observed in the rats treated with E 2 .…”

Section: Discussionmentioning

confidence: 99%

Estrogenic effects of silymarin in ovariectomized rats

Kummer¹,

Mašková²,

Čanderle³

et al. 2001

Vet. Med. - Czech

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The objective of this study was to test whether silymarin induces changes indicative of estrogenic effects in gonadal organs of ovariectomized (OVX) rats. Silymarin was administered in two experimental groups of OVX rats (n = 7 + 7) for 30 days at the doses of 25 or 50 mg per animal per day. OVX rats (n = 7) receiving 5 µg of 17b-estradiol (E2) for the last three days before killing and untreated OVX rats (n = 7) were used as the positive and the negative controls, respectively. Uterine and blood samples were collected immediately after killing. Compared with the negative controls, total and normalized uterine weights were significantly higher in the two experimental groups (P < 0.01 and P < 0.05, respectively). Uterotrophic effects of silymarin were also evident from increased heights of the luminal epithelium (P < 0.01) and the endometrium (P < 0.05). The response was dose-independent within the tested range. The strongest uterine response was observed in the OVX rats treated with E2. A highly significant decrease in mean density of estrogen receptor (ERa) immunostaining in the luminal and the glandular endometrial epithelia (P < 0.01) and a stronger ERa immunostaining in stromal cells were observed in the two experimental and the positive control groups. The activities of alkaline and acid phosphatases were significantly increased in the luminal (P < 0.05) and the glandular (P < 0.01) epithelia only in the rats treated with E2. Both silymarin and E2 induced an increase in thyroid hormone concentrations in blood serum. The rises of free T3 and T4 were significant (P < 0.05) in the group receiving 50 mg of silymarin per day. Hepatic oxidative metabolism of steroids was assumed to be another target of the action of silymarin. The mitochondrial cytochrome P450-dependent testosterone hydroxylase activity and the cytochrome P4501A-dependent 7-ethoxyresorufin O-deethylase activity were significantly increased (P < 0.05) in the group receiving 50 mg of silymarin per day and in the E2-treated control group, respectively. However, the modulations of the CYP enzymes played only a minor role in the overall estrogenic effect of silymarin. Histological and functional alterations in the OVX rats treated orally with silymarin for 30 days were consistent with those seen in E2-treated rats and were indicative of estrogenic effects of silymarin.

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Effect of Oestradiol on Cell Proliferation and Histological Changes in the Uterus and Vagina of Mice

Cited by 104 publications

References 0 publications

Strain differences in vaginal responses to the xenoestrogen bisphenol A.

Strain differences in vaginal responses to the xenoestrogen bisphenol A.

Differential distribution of oestrogen receptor-alpha and -beta mRNAs in the female reproductive organ of rats as revealed by in situ hybridization

Estrogenic effects of silymarin in ovariectomized rats

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