OBJECTIVETo study 17β-estradiol (E2), ethinylestradiol (EE2), estriol (E3), estrone (E1) on MCF-7 proliferation effects, and compare the effects of independent action (IA) model with concentration addition (CA) model in assessing the combined effects of estrogen.

METHODSThe combinations of E2 + EE2, E2 + E3 and E2 + E1 were chosen and the cellular proliferation effects were examined by MTT assay.

RESULTSThe maximum proliferation effects at dose of 10⁻⁹ mol/L was 325.48% for E2, 330.34% for EE2, 255.22% for E3, and 199.61% for E1. In the E2 + EE2, E2 + E3, E2 + E1 groups, the results of IA model analysis were very close to the experimental results. The IA model tend to overestimated the experimental results, while the CA model often underestimated the experimental results. In the EC (E2, 30) + C (EE2, 70) group, the results exceed the maximum estrogen effects of E2, while in other groups, the results were lower.

CONCLUSIONSThe estrogenic effects of the four tested substances from high to low efficiency were that: EE2 > E2 > E3 > E1. The effect of IA model in predicting the combined effects of binary mixture was better than CA model. A small proportion of binary mixture showed synergy.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Estradiol ; pharmacology ; Estriol ; pharmacology ; Estrogens ; pharmacology ; Estrone ; pharmacology ; Ethinyl Estradiol ; pharmacology ; Female ; Humans

OBJECTIVETo assess the single and combined effects of estrone (E1) and 17β-estradiol (E2) on goldfish (Carassius auratus).

METHODSBatch tests were conducted. Serum levels of vitellogenin (VTG) and E2, gonadosomatic indices (GSI), gonadal DNA damage and liver 7-ethoxyresorufin-O-deethylase (EROD) activity were measured after exposure for 14 days.

RESULTSThe VTG level increased significantly in a concentration-dependent manner. The serum E2 level was significantly higher and the GSI level was significantly lower in goldfish after exposed to the 3 drugs. DNA damage occurred in treated samples and EROD activity was significantly suppressed 7 days after exposure. The joint effect of E1 and E2 was additive with regard to VTG induction.

CONCLUSIONThe results of our study highlight a series of effects of steroidal estrogens on goldfish. Further study is needed to confirm their effect as a whole.

Animals ; Cytochrome P-450 CYP1A1 ; metabolism ; DNA Damage ; drug effects ; Drug Combinations ; Estradiol ; pharmacology ; Estrone ; pharmacology ; Goldfish ; Gonads ; drug effects ; metabolism ; Male ; Vitellogenins ; blood

The purpose of this study was to determine the effects of piperazinyl estrone, a new estrogen derivative, on bone turnover, bone mass and uterine weight in female aged rats. Thirty-two Sprague-Dawley female rats at the age of 22 months were treated with vehicle or with piperazinyl estrone (P-E) at 0.5, 1 and 2 mg/kg/day, subcutaneous injection for 1 month. At the time of death, the uterine weight was measured and bone histomorphometric analysis of proximal tibial metaphyses (PTM) was performed in undecalcified sections. Compared with control, bone mass was increased in P-E groups. Dynamic data showed that bone resorption were decreased, but bone formation was not declined and bone mass was increased significantly in P-E (1 mg/kg day) group. There was no significant change in uterine weight. The findings of this study show that piperazinyl estrone at dosage of 1 mg/kg/d is most efficacious in preventing the bone losses in aged rats and has no side effect on uterus.
Aging ; Animals ; Estrone ; adverse effects ; analogs & derivatives ; pharmacology ; Female ; Osteogenesis ; drug effects ; Osteoporosis ; prevention & control ; Rats ; Rats, Sprague-Dawley ; Uterus ; drug effects

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

AIMTo study the effect of XW630 on expression of pro-oncogene c-myc in the long bones of fetal mice in vitro for postulating the mechanism by which XW630 exerts its effect on bone.

METHODSThe fetuses of pregnant mice were removed on day 16 of gestation, the long bones of the forelimbs of female fetal mice were freed of muscle and soft tissue and cultured in a specific device for 48 h in BGJb medium treated with 1 x 10(-7), 1 x 10(-8) and 1 x 10(-9) mol.L-1 XW630 in the final medium. After cultured for 48 h, the long bones were harvested and immunohistochemical analysis was performed for determination of c-Myc protein expression in epiphyseal plates. The areas of positive cells in the resting zone, proliferative zone and hypertrophic zone in epiphyseal plate were determined under image analytic system.

RESULTSWhen the concentration of XW630 in the medium was 1 x 10(-9) mol.L-1, the area of c-Myc positive cells increased in the proliferative zone compared with 1 x 10(-9) mol.L-1 in the estrone group, significant increase was also observed in the resting zone compared with the control group. When the concentration of XW630 in medium was 1 x 10(-8) or 1 x 10(-7) mol.L-1, stronger expression than that in the control group and the estrone group at the same concentration was observed in each of the three zones.

CONCLUSIONThe estrogenic effect of XW630 on bone was stronger than that of estrone. XW630 may promote proliferation and differentiation of chondroncytes by promoting c-Myc protein expression in chondroncytes. Thus, endochondral bone formation was enhanced.

Animals ; Chondrocytes ; metabolism ; Culture Techniques ; Estrone ; pharmacology ; Female ; Fetus ; Mice ; Piperazines ; pharmacology ; Pregnancy ; Proto-Oncogene Proteins c-myc ; metabolism ; Tetracyclines ; pharmacology ; Ulna ; drug effects ; metabolism ; Up-Regulation ; drug effects

AIMTo determine the effect of piperazinyl estrone, a new estrogen derivative, on bone turnover, bone mass and uteri in ovariectomized rats.

METHODSFemale Sprague-Dawley rats were ovariectomized (OVX) or sham operated (sham) at the age of 3 months and treated with estrone (E) at 0.75 mg.kg-1.d-1, or with piperazinyl estrone (P-E) at 1 or 10 mg.kg-1.d-1, orally, for 3 months. At the time of death, the uterine weight was measured. Bone histomorphometric analysis of proximal tibial metaphyses (PTM) was performed in undecalcified sections.

RESULTSBone histomorphometric data showed that the percent trabecular area (% Tb.Ar) of OVX rats with bone high turnover was significantly decreased. The uteri were atrophied. The percent trabecular area (% Tb.Ar) of estrone treated group was increased in decreasing bone turnover manner. But the size and weight of uteri in this group were increased vs OVX group. The bone loss induced by OVX was preserved by P-E treatment, but the mechanism of maintaining bone is different from that of E-treated rats. P-E treatment in low dose did not decrease any bone formation indices, such as percent labeling perimeter, bone formation rate per bone volume (BFR/BV), except bone mineral apposition rate (MAR) compared with E-treated group, and maintained them at OVX level. The uteri were found to be in atrophy compared with the match dose (0.75 mg) of E-treated OVX rats. But rats treated with high dose of P-E showed the same change like E-treated group.

CONCLUSIONThe finding of this study shows that lower dosage of piperazinyl estrone has effect on preventing the bone losses in OVX rats, while the bone formation and the uterus are not affected, thus supporting the hypothesis that piperazinyl estrone has the potential to prevent postmenopausal bone loss in women with less side effects.

Animals ; Atrophy ; prevention & control ; Bone Density ; Estradiol Congeners ; pharmacology ; therapeutic use ; Estrone ; analogs & derivatives ; pharmacology ; therapeutic use ; Female ; Organ Size ; drug effects ; Osteogenesis ; drug effects ; Osteoporosis ; prevention & control ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Uterus ; pathology