Estrogen impacts neural development; meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.
Receptors, Estrogen/metabolism* ; Estrogens ; Benzhydryl Compounds/pharmacology* ; Nervous System/metabolism*

Bone Resorption ; China ; Cytokines ; physiology ; Diphosphonates ; pharmacology ; Estrogens ; pharmacology ; Humans ; Jaw ; drug effects ; metabolism

BACKGROUNDThere are definite gender differences in patients with macular holes. Menopausal women over 50 years are most affected. We aimed to observe the effect of estrogen on collagen gel contraction by cultured human retinal glial cells. It is speculated that estrogen could strengthen the tensile stress of the macula by maintaining the correct morphology and contraction.

METHODSEstrogen was used to determine its effects on collagen gel contraction, and its function was measured using morphological changes in cells. Human retinal glial cells were cultured in collagen solution. The cells were then exposed to collagen gels and the degree of contraction of the gel was determined.

RESULTSEstrogen at differing concentrations had no effect on the growth of human retinal glial cells. However, after exposed to collagen gel block, less contraction was noted in the estrogen-treated group than in the control group.

CONCLUSIONSEstrogen can inhibit collagen gel contraction by glial cells. These results suggest a mechanism for macular hole formation, which is observed in menopausal females.

Cells, Cultured ; Collagen ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Estrogens ; pharmacology ; Female ; Humans ; Neuroglia ; drug effects ; metabolism

OBJECTIVETo explore the effects of environmental estrogens (n-4-noniphenol, NP; bisphenol, BisA; and dibutylphthalate, DBP) on apoptosis induced by estrogen depletion in breast cancer T47D cells.

METHODSHuman T47D breast cancer cells were grown in DMEM medium containing 10% bovine serum. Four days before adding the test compounds, the cells were washed in phosphate-buffered saline, and the medium was substituted with a phenol red-free DMEM medium containing 5% dextral charcoal-stripped FBS. Respective test compound was added in fresh medium and the control cell received only the vehicle (ethanol). Apoptotic features in T47D cell were analyzed by light microscope that was commonly used to define apoptosis. DNA integrity of T47D cells was examined by agarose gel electrophoresis. Hypodiploid population was detected by flow cytometry.

RESULTSThe typical characters of apoptosis in T47D cells were observed after estrogen deletion and then disappeared following exposure to T47D cells at 32 x 10(-7) mol/L Np and 32 x 10(-7) mol/L BisA respectively. Inhibition of apoptosis at 32 x 10(-6) mol/L DBP was not shown in our study.

CONCLUSIONN-4-noniphenol and Bisphenol A could inhibit apoptosis induced by estrogen deletion in breast cancer T47D cells. This result suggests that these environmental estrogens might involve in signal transduction connected with apoptosis.

Apoptosis ; drug effects ; Benzhydryl Compounds ; Cell Line, Tumor ; drug effects ; metabolism ; Dibutyl Phthalate ; pharmacology ; Estrogens ; deficiency ; Estrogens, Non-Steroidal ; pharmacology ; Female ; Flow Cytometry ; Humans ; Phenols ; pharmacology

Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the present study, we examined the neuroprotective spectrum of estrogen against excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25-35. However, all these neuroprotective effects were mediated by the anti-oxidative action of estrogens. When oxidative stress was blocked by an antioxidant trolox, estrogens did not show any additional protection. Addition of a specific estrogen receptor antagonist ICI182,780 did not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injuries mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors mediate neuroprotection.
Amyloid beta-Protein/pharmacology ; Animal ; Antioxidants/pharmacology* ; Antioxidants/metabolism ; Apoptosis/drug effects* ; Cells, Cultured ; Chelating Agents/pharmacology ; Chromans/pharmacology ; Estradiol/pharmacology ; Estrogens/pharmacology* ; Estrogens/metabolism ; Estrone/pharmacology ; Ethylenediamines/pharmacology ; Excitatory Amino Acid Agonists/pharmacology ; Ferric Compounds/pharmacology ; Lactate Dehydrogenase/analysis ; Mice ; N-Methylaspartate/pharmacology ; Neurons/metabolism ; Neurons/drug effects* ; Neurons/cytology ; Organ of Corti/cytology ; Peptide Fragments/pharmacology ; Staurosporine/pharmacology

Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the present study, we examined the neuroprotective spectrum of estrogen against excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25-35. However, all these neuroprotective effects were mediated by the anti-oxidative action of estrogens. When oxidative stress was blocked by an antioxidant trolox, estrogens did not show any additional protection. Addition of a specific estrogen receptor antagonist ICI182,780 did not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injuries mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors mediate neuroprotection.
Amyloid beta-Protein/pharmacology ; Animal ; Antioxidants/pharmacology* ; Antioxidants/metabolism ; Apoptosis/drug effects* ; Cells, Cultured ; Chelating Agents/pharmacology ; Chromans/pharmacology ; Estradiol/pharmacology ; Estrogens/pharmacology* ; Estrogens/metabolism ; Estrone/pharmacology ; Ethylenediamines/pharmacology ; Excitatory Amino Acid Agonists/pharmacology ; Ferric Compounds/pharmacology ; Lactate Dehydrogenase/analysis ; Mice ; N-Methylaspartate/pharmacology ; Neurons/metabolism ; Neurons/drug effects* ; Neurons/cytology ; Organ of Corti/cytology ; Peptide Fragments/pharmacology ; Staurosporine/pharmacology

OBJECTIVEEstrogen is closely associated with hypospadias. The present study was to explore the molecular mechanism of hypospadias caused by estradiol.

METHODSFibroblasts obtained from the prepuce of hypospadiac and normal children were cultured in vitro and treated with 17-beta ethinyl estradiol (17-EE) at the concentrations of 1 micromol/L to 0.1 nmol/L for 2 hours, or at 0.1 micromol/L for 0.5, 1, 2, 4, 8, 16 and 24 hours. MTT assay was used to evaluate the effect of 17-EE on the proliferation of the cells, and RT-PCR was employed to detect the expressions of the activating transcription factor-3 (ATF3) and connective tissue growth factor (CTGF) in the hypospadiac tissue. The results were compared with those obtained from the nonhypospadiac tissue.

RESULTSThe expressions of ATF3 and CTGF were significantly upregulated in the hypospadiac tissue as compared with the nonhypospadiac group. At the concentration of 1 micromol/L, 17-EE significantly inhibited the proliferation of the cells. ATF3 mRNA was elevated at 1-2 hours, while CTGF mRNA showed no significant changes in 24 hours.

CONCLUSIONATF3 and CTGF are two candidate genes involved in the etiology of hypospadias. And estradiol may induce hypospadias by upregulating the expressions of ATF3 and CTGF.

Activating Transcription Factor 3 ; genetics ; metabolism ; Cells, Cultured ; Child ; Connective Tissue Growth Factor ; genetics ; metabolism ; Estradiol ; pharmacology ; Estrogens ; pharmacology ; Fibroblasts ; metabolism ; Foreskin ; metabolism ; Humans ; Hypospadias ; genetics ; metabolism ; Male

To evaluate the estrogenic activities of several chemicals such as 17 beta-estradiol (E2), rho-nonylphenol, bisphenol A, butylparaben, and combinations of these chemicals, we used recombinant yeasts containing the human estrogen receptor [Saccharomyces cerevisiae ER + LYS 8127]. We evaluated E2 was most active in the recombinant yeast assay, followed by rho-nonylphenol, bisphenol A, butylparaben. The combinations of some concentrations of 17-estradiol as a strong estrogen and bisphenol A or butylparaben as a weak estrogen showed additive estrogenic effects. Also, the combinations of some concentrations of nonlyphenol and butylparaben and combination of butylparaben and bisphenol A showed additive effects in the estrogenic activity. Therefore, the estrogenic activities of the combinations of two chemicals were additive, not synergistic.
Cloning, Molecular ; Estradiol/pharmacology ; Estrogens/classification/*pharmacology ; Estrogens, Non-Steroidal/*pharmacology ; Humans ; Kinetics ; Parabens/pharmacology ; Phenols/pharmacology ; Receptors, Estrogen/drug effects/*physiology ; Recombinant Proteins/drug effects/metabolism ; Saccharomyces cerevisiae/genetics

BACKGROUNDEstrogen deficiency causes atrophic changes within the urogenital tract, and is associated with urinary symptoms. The purpose of this study was to investigate the effects of estrogen and tibolone on bladder histology, and the changes of estrogen receptor alpha and beta (ERalpha and beta) protein expression in the detrusor muscle.

METHODSForty female rats were separated into four groups of ten each. They received a sham operation (Sham), ovariectomy (Ovx), ovariectomy plus estrogen replacement (Ovx + E), or ovariectomy plus tibolone treatment (Ovx + T). After 12 weeks each rat was anesthetized and the bladders were removed. The bladders' ultra structure, collagen fiber (CF) to smooth muscle (SM) ratio and ER subtypes were studied. Statistical analyses were performed using the one-way analysis of variance test.

RESULTSOvx resulted in significant degeneration in bladder ultra structure; however, estrogen and tibolone reversed those changes. Ovx increased the CF/SM ratio, estrogen and tibolone resulted in an increase. Two estrogen receptors (ERs) were expressed in the bladder detrusor, with ERbeta the main subtype. Ovx resulted in up-regulation of ERalpha and down-regulation of ERbeta. With estrogen and tibolone treatment, ERbeta showed a significant increase but ERalpha showed no significant difference compared with Ovx.

CONCLUSIONSEstrogen deficiency deteriorates bladder ultra structure and histology. Supplementary estrogen can improve bladder function which may be due to inhibition of collagen hyperplasia and increased SM density. ERbeta has an important role in mediating estrogen function in the bladder. Tibolone has a mild estrogenic action and has an effect on bladder function and structure to some degree.

Animals ; Estrogen Receptor Modulators ; pharmacology ; Estrogens ; pharmacology ; Female ; Immunohistochemistry ; Microscopy, Electron, Transmission ; Norpregnenes ; pharmacology ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Receptors, Estrogen ; metabolism ; Urinary Bladder ; drug effects ; metabolism ; ultrastructure

OBJECTIVEThe objective of this study was to investigate the estrogenic activity of genistein and zearalenone through their effects on the proliferative capacity of human ovarian PEO4.

METHODSEstrogen receptor-positive PEO4 cell was grown in DMEM medium containing 10% bovine serum. Five days before the addition of the test compounds, the cells were washed in phosphate-buffered saline, and the medium was substituted with a phenol red-free DMEM medium containing 5% dextran charcoal-stripped FBS. The respective test compound was added in fresh medium and the control cell received only the vehicle (ethanol). Cell proliferation was detected respectively by MTT assay, (3)H-TdR incorporation and flow cytometry.

RESULTSCompared with vehicle control, 96 x 10(-6) mol/L GS significantly inhibited PEO4 cell proliferation and DNA synthesis as measured by MTT and (3)H-TdR incorporation after treatment for 24 h. Alao, 32 x 10(-6) mol/L GS could exert inhibition on PEO4 cell growth as time extension to 48 h. 32 x 10(-6) mol/L approximately 96 x 10(-6) mol/L GS induced G(2)/M arrest. At low dose (< 8 x 10(-6) mol/L=, GS promoted proliferation in PEO4 cells. ZEA enhanced proliferation, promoted DNA synthesis and increased the S phase population in PEO4 cells.

CONCLUSIONSGenistein possess estrogenic activity and zearalenone have anti-estrogenic activity. They play different effects on the proliferation of human ovarian cancer cell. Genistein enhanced the proliferation of PEO4. Zearalenone inhibited its the proliferation. These results implied that genistein and zearalenone elicit different signal-transduction channel.

Antineoplastic Agents ; pharmacology ; Cell Division ; drug effects ; Estrogens, Non-Steroidal ; pharmacology ; Female ; Genistein ; pharmacology ; Humans ; Ovarian Neoplasms ; pathology ; Receptors, Estrogen ; metabolism ; Tumor Cells, Cultured ; Zearalenone ; pharmacology