The cardiac electrophysiological effects of genistein (GST) were examined in guinea pig papillary muscle using intracellular microelectrode technique. The results obtained are as follows. (1) Duration of action potential (APD) in normal papillary muscles was decreased by GST (10 100 micromol/L) in a concentration-dependent manner. (2) In partially depolarized papillary muscles, 50 micromol/L GST not only reduced APD, but also decreased the amplitude of action potential, overshoot and maximal velocity of phase 0 depolarization. (3) Pretreatment with N( )-nitro-L-arginine (L-NNA, 5 mmol/L) failed to affect the above effects of GST (50 micromol/L)on papillary muscles. (4) 17beta-estradiol (E(2), 5 micromol/L) or GST (10 micromol/L) alone did not affect action potential, while GST combined with E(2) at the same doses shortened APD significantly. All these results indicate that the effects of GST on papillary muscles are likely due to a decrease of calcium inflow which is not mediated by NO and that GST has a facilitative or synergetic action with E(2).
Action Potentials ; drug effects ; Agmatine ; pharmacology ; Animals ; Dose-Response Relationship, Drug ; Drug Synergism ; Electrophysiology ; Estradiol ; pharmacology ; Estrogens, Non-Steroidal ; pharmacology ; Female ; Genistein ; pharmacology ; Guinea Pigs ; Isoflavones ; Male ; Papillary Muscles ; drug effects ; physiology ; Phytoestrogens ; Plant Preparations

OBJECTIVETo study the effects of phytoestrogen alpha-zearalanol (alpha-ZAL) on normal human breast.

METHODSTen specimens of normal human breast tissues were subcutaneously implanted into 30 athymic nude mice aged 9-10 weeks, one for 3 mice. These mice were then randomly divided into three groups: control group (without hormone treatment, n = 10), 1 mg/kg alpha-ZAL group (n = 10), and 5 mg/kg alpha-ZAL group (n = 10). All breast tissues were taken out 6 weeks later. Immunohistochemistry was used to determine the protein expressions of proliferating cell nuclear antigen (PCNA), inhibiting apoptosis gene Bcl-2, estrogen receptor (ER), and progesterone receptor (PR). Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expression levels of estrogen sulfotransferase (EST) mRNA and bridging integrator protein-1 (BIN1) mRNA. Morphological features of grafts before and after treatment were also observed.

RESULTSAlpha-ZAL had no significant effects on Bcl-2, PCNA, ER, and PR expression of mammary epithelial cells in graft specimens. Alpha-ZAL upregulated BIN1 mRNA expression in grafts, but had no significant effect on ESTmRNA expression.

CONCLUSIONSAlpha-ZAL does not affect the morphology, proliferating, and apoptosis of epithelial cells in normal human breast tissues implanted into nude mice, but it may increase the gene expression of tumor-inhibiting BIN1, suggesting that alpha-ZAL may have potential proteotive effect on normal human breast.

Adult ; Animals ; Breast ; chemistry ; drug effects ; Estrogens, Non-Steroidal ; pharmacology ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Phytoestrogens ; pharmacology ; Proliferating Cell Nuclear Antigen ; analysis ; Random Allocation ; Receptors, Estrogen ; analysis ; Receptors, Progesterone ; analysis ; Zeranol ; pharmacology

Animals ; Coronary Disease ; prevention & control ; Dibutyl Phthalate ; adverse effects ; Dioxins ; adverse effects ; Environmental Pollutants ; adverse effects ; Estrogens, Non-Steroidal ; pharmacology ; Humans ; Isoflavones ; pharmacology ; Phytoestrogens ; Plant Preparations ; pharmacology ; Zearalenone ; adverse effects

It is known that inflammatory processes result from intraocular surgery or ocular trauma mediated by prostaglandin, which cause the protein amounts to increase in anterior chmaber, congestion of vessels, miosis and intraocular pressure to increase. In order to compare the anti-inflammatory effects of antiprostaglandin agents such as Aspegic(R), Profenal(R) and Ocufen(R) in 40 eyes of 20 rabbits, we measured the pupil diameter and amounts of PG E2 and total protein before and after paracentesis. The inhibitory effects of Aspegiz(R), Profenal(R) and Ocufen(R) to pupillary constnztion were significantly greater (p<0.05) than control. The lowering effect to PG E2 and total protein were greater in Aspegic(R), Profenal(R) and Ocufen(R) than control. Through over experiment we suggested that the topical non-steroidal anti-inflammatory agents such as Aspegic(R), Profenal(R), and Ocufen(R) can inhibit the PG activator in antivator chamber and interrupt the miosis and rising intraocular pressure during surgery.
Anterior Chamber* ; Anti-Inflammatory Agents, Non-Steroidal* ; Estrogens, Conjugated (USP) ; Intraocular Pressure ; Miosis ; Paracentesis* ; Pupil ; Rabbits*

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

OBJECTIVETo explore the phytoestrogenic effects of ten kinds of Chinese medicine including flos carthami, radix cyathulae, radix salviae miltiorrhizae, fructus ligustri lucidi, fructus lycii, radix clycyrrhizae, herba cistanches, herba epimedii, fructus psoraleae and semen cuscutae.

METHOD240 female Kunming mice weighting 9 - 12 g were randomly divided into two main groups A and B. A group was divided into 12 small groups: 1 solvent control group, 1 diethylstilbestrol control group and 10 Chinese medicine groups. B group was also divided into 12 small groups: 1 solvent control group, 1 diethylstilbestrol control group and 10 Chinese medicine antagonistic groups. Mice in ten antagonistic groups were administered both Chinese medicine and diethylstilbestrol everyday. After administered(op) for 4 days, blood was collected and serum was separated. The effect of the pharmacological serum on proliferation rate of MCF-7 (ER+) was analyzed by MTT-assay.

RESULTIn A group, proliferation rates of MCF-7 cells treated with serum from eight Chinese medicine groups including flos carthami, radix cyathulae, radix salviae miltiorrhizae, fructus lycii, herba cistanches, herba epimedii, fructus psoraleae and semen cuscutae were coued markedly increase respectively. While serum from fructus ligustri lucidi group could markedly decrease the proliferation rate of MCF-7 cells. In B group, the increased proliferation rate of MCF-7 cells caused by diethylstilbestrol was significantly reduced in seven Chinese medicine antagonistic groups including flos carthami, radix cyathulae, radix salviae miltiorrhizae, radix clycyrrhizae, herba epimedii, fructus psoraleae and semen cuscutae. While the increased proliferation rate could be markedly enhanced in herba cistanches group.

CONCLUSIONSix kinds of Chinese medicine such as flos carthami, radix cyathulae, radix salviae miltiorrhizae, herba epimedii, fructus psoraleae and semen cuscutae show both estrogenic effects (when administered indepently) and antiestrogenic effects (when administered together with diethylstilbestrol). Such bidirectional effects depends on the internal estrogen level.

Animals ; Breast Neoplasms ; metabolism ; pathology ; Carthamus tinctorius ; chemistry ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Diethylstilbestrol ; pharmacology ; Drug Antagonism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Estrogens, Non-Steroidal ; pharmacology ; Female ; Humans ; Mice ; Phytoestrogens ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Random Allocation ; Receptors, Estrogen ; metabolism ; Salvia miltiorrhiza ; chemistry ; Serum

BACKGROUND: The effects of sex hormones on nociception and the analgesic actions of non-steroidal anti-inflammatory drugs (NSAIDs) in an acute arthritic pain model were investigated. METHODS: Rats were ovariectomized and randomly assigned to three experimental groups. The estrogen group (n = 45) received a 0.25 mg pellet of 17beta-estradiol, the placebo group (n = 45) received a 0.25 mg pellet of a placebo and the progesterone group (n = 45) received a 25 mg pellet of progesterone. Arthritis was induced by injecting 2% carrageenan into the knee joint cavity of the right hind leg. Before and after the injection, rats were allowed to walk freely through a weight load apparatus. The weight load and the weight of the rat were measured for each test. One hour after injection, ibuprofen or NS-398, dissolved in dimethyl sulfoxide, was injected intraperitoneally (1 mg/kg/ml). RESULTS: The carrageenan injection into the knee joint cavity of the right hind leg of the rat resulted in a significant decrease in the weight load on the injected leg. Estrogen-treated rats showed lower weight load reduction than the placebo and progesterone groups, NS-398 increased the weight load compared to rats not receiving NSAIDs. CONCLUSIONS: These results suggest that the nociceptive response after acute inflammation was reduced by estrogen, and that only NS-398 had a good analgesic effect in the placebo and progesterone groups. It is likely that the analgesic effect of NSAIDs on the estrogen group was unremarkable compared to those of the placebo and progesterone groups because of the antinociceptive action of estrogen.
Animals ; Anti-Inflammatory Agents ; Anti-Inflammatory Agents, Non-Steroidal* ; Arthritis ; Carrageenan ; Dimethyl Sulfoxide ; Estrogens ; Gonadal Steroid Hormones* ; Ibuprofen ; Inflammation ; Knee Joint ; Leg ; Nociception* ; Progesterone ; Prostaglandin-Endoperoxide Synthases ; Rats

Bisphenol A (BPA) is a commonly used phenolic environmental estrogen. Long-term exposure of female mammalians to BPA can lead to endocrine disorders, followed by the morphological and functional changes in ovary, uterus, vagina, and oviducts. The interactions of BPA with various target molecules or tissues will cause different effects. To further elucidate the effects of BPA on female reproductive system, we review the changes in the structure and functions of female reproduction system after BPA exposure and their possible mechanisms.
Benzhydryl Compounds ; toxicity ; Endocrine Disruptors ; toxicity ; Estrogens, Non-Steroidal ; toxicity ; Female ; Humans ; Ovary ; drug effects ; Phenols ; toxicity ; Uterus ; drug effects ; Vagina ; drug effects

AIMTo assess the effect of estradiol-17beta (E(2)) and bisphenol A (BPA) administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups' reproductive system in ICR mice.

METHODSFemale mice were implanted with a tube filled with 10 ng, 500 ng, 1 microg, or 10 microg of E(2), or 100 microg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E(2) was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 microg/day.

RESULTSMost of the mice given 1 microg and 10 microg of E(2) did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights (testes, epididymides and accessory reproductive glands) in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E(2) and 5 mg of BPA than that in the control.

CONCLUSIONChronic exposure to E(2) and BPA might disrupt spermatogenesis in male pups.

Animals ; Benzhydryl Compounds ; Birth Rate ; Estradiol ; pharmacology ; Estrogens, Non-Steroidal ; pharmacology ; Female ; Genitalia, Male ; drug effects ; pathology ; Lactation ; Male ; Mice ; Phenols ; pharmacology ; Pregnancy ; Spermatogenesis ; drug effects

AIMTo study the effect of prenatal exposure to diethylstilbestrol (DES) and the role of actin and proliferating cell nuclear antigen (PCNA) on testicular gubernaculum development in fetal male Kunming mice.

METHODSPregnant mice were randomly assigned to 6 groups and injected with DES subcutaneously from gestational day 9 (E9) to day 17 (E17) at doses of 0, 25, 50, 100, 200 microg.kg-1.d-1 in 0.2 mL dimethyl sulfoxide (DMSO). On E17 they were sacrificed and fetuses quickly removed for fixation. Male fetuses were sliced on serial coronal plane. Histological changes were observed under the light microscope (LM) and ultrastructural changes with the scanning and transmission electron microscopes (SEM and TEM). The expression intensity of actin and PCNA in the gubernacula was quantitated by immunohistochemistry.

RESULTSThe mortality of the fetuses was higher in the DES-treated groups than that in the DMSO and saline controls (P<0.05). Under LM the gubernacula were seen to be poorly developed with smaller bulbs. On SEM the bulbs lose the clear demarcation between the mesenchymal inner core and the muscular outer layer and looked like a small cone instead of the normal cylindrical appearance. On TEM there were some smaller disordered myofibrils and sparse cytoplasmic organelles in the gubernacular muscular cells of the treated groups. The expression intensity of actin and PCNA in the gubernacula was significantly weaker in the treated groups than that in the DMSO and saline controls (P<0.05).

CONCLUSIONDES induces underdevelopment of the gubernacula in a dose-dependent manner in fetal male mice and down regulates the actin and PCNA expression.

Animals ; Diethylstilbestrol ; pharmacology ; Dose-Response Relationship, Drug ; Estrogens, Non-Steroidal ; pharmacology ; Female ; Fetal Death ; chemically induced ; Immunohistochemistry ; Male ; Mice ; Microscopy, Electron, Scanning ; Pregnancy ; Testis ; cytology ; drug effects ; embryology