• Korean Journal of Veterinary Research
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• v.27 no.1
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• pp.9-17
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• 1987

The present study has been carried out to elucidate the antiestrogenic effects of tamoxifen in immature rat uterus. The content of DNA and protein and uterine wet weight were measured after the injections of $5{\mu}g$ of estradiol-$17{\beta}$, $50{\mu}g$ of tamoxifen, a combination of both, or vehicle only subcutaneously. The results obtained were summarized as follows: 1. DNA content in uterus was increased at 48 hours after estradiol-$17{\beta}$ or tamoxifen injection (p<0.01). 2. The increament rate of uterine DNA content was significantly (p<0.01) lower in tamoxifen treated group than that in estradiol-$17{\beta}$ treated group. 3. Antiestrogenic effect of tamoxifen on protein content in uterus was apparent at 72 hours after simultaneous administration of both drugs. 4. The uterine wet weight was started to increase at three hours after the injection of estradiol-$17{\beta}$ or tamoxifen. 5. While estradiol-$17{\beta}$ increased steadily uterine wet weight up to 138.5mg at 72 hours after the injection, but tamoxifen failed to increase it after 48 hours. Tamoxifen inhibited significantly (p<0.01) the effect of estradiol-$17{\beta}$ on it thereafter.

• Journal of Embryo Transfer
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• v.3 no.1
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• pp.13-23
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• 1988

These studies were undertaken to examine the interaction of tamoxifen with sex steroid hormones in rat uterine activity. The uterine wet weights of the immature Tat uterus were examined after the administration of estradiol-l7$\beta$(1$\mu$g), tamoxifen(50$\mu$g), progesterone(lmg). The uterotropic activity in immature ovariectomized rats was observed under various treatment conditions following pretreatment with above drugs. The results obtained were as follows:1) Tamoxifen produced significant increase (p <0.01) in uterine wet weight compared with control group, although the increase was not as great as that seen with estradiol-17$\beta$. Administration of estradiol-17$\beta$ together with tamoxifen inhibited significantly the increase of uterine wet weight by estradiol-17$\beta$ (p < 0.01). Coadministration of progresterone with tamoxifen partly blocked the increase of tamoxifen-induced uterine wet weights by progesterone. 2) Estradiol-17$\beta$after the estradiol-17$\beta$ pretreatment discontinued the declining uterine wet weights due to the absence of estrogen support, but uteri continued to increase in weight if daily estradiol-17 $\beta$ was maintained. Administration of tamoxifen on the fourth day of estradiol-17$\beta$ treatment reduced uterine wet weights within 24 hours, and the weights continued to decline with additional tamoxifen. 3) The modest growth of the uterus induced by three daily injections of 5Opg tamoxifen remained stable for five days, with or without additional tamoxifen treatment. Coadministration of tamoxifen with estradiol17$\beta$ increased slightly the increase of uterine wet weight by tamoxifen. Coadministration of tamoxifen with progesterone inhibited the increase of uterine wet weight by tamoxifen. 4) The modest growth of the uterus induced by three daily injections of lmg progesterone reduced uterine wet weight to the control level for five days. Commencement of tamoxifen or estadiol-17 $\beta$ injections on the fourth day of progesterone treatment rapidly elevated uterine wet weight.

• Toxicological Research
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• v.16 no.3
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• pp.201-209
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• 2000

In association with the international validation program to establish a rodent uterotrophic assay, we conducted preliminary uterotrophic assay proposed by GECD using immature female rats. In the present study, oral and subcutaneous routes were chosen to compare the effects of estrogenic com-pounds in the two dosing regimens. The reference compound ethinyl estradiol (EE) and the antagonist ZM189154(ZM) were administered by gavage or subcutaneously (s.c.) to immature female SD rats from 20 to 22 days of age. For each study, sixty-six female rats were randomly assigned to eleven groups: Untreated control, EE 0,0.01, 0.03, 0.1, 0.3, 1.0,3.0 and 10.0 $\mu\textrm{g}$/kg, EE 3.0 $\mu\textrm{g}$/kg(gavage)/0.3 $\mu\textrm{g}$/kg(s.c) & ZM 0.1 mg/kg, and EE 3.0 $\mu\textrm{g}$/kg(gavage)/0.3 $\mu\textrm{g}$/kg (s.c) & ZM 1.0 mg/kg. There were no treatment-related changes in clinical signs, body weights, food consumption, and necropsy findings in any groups of two studies. The wet and blotted uterus weights increased dose-dependently. Histopathological examination revealed that diameter of uterine duct, height of uterine luminal epithelium. and height oj vaginal epithelium increased dose-dependently. The proliferating cell nuclear antigen (PCNA) immunoreactive cells were increased in number dose-dependently. The estrogenic effects observed in the present studies occurred at $\geq$ 0.3 $\mu\textrm{g}$/kg of oral dose and $\geq$ 0.1 $\mu\textrm{g}$/kg of s.c. dose. An antagonistic effect of ZM against EE was found in both uterus weight and histopathological parameters. From the results obtained, it can be concluded that dose-dependence of the uterotrophic assay using EE and ZM was well demonstrated by gavage and subcutaneous administration and that the estrogenic effects of EE by s.c. dose were higher than those by gavage administration. In addition, blotted uterus weight was more sensitive than wet uterus weight and vaginal epithelial height was found to be the most sensitive parameter among the parameters examined.

• Nutrition Research and Practice
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• v.8 no.3
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• pp.292-296
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• 2014

BACKGROUND/OBJECTIVES: This study was conducted to assess the potential of St. John's Wort (Hypericum perforatum) to prevent obesity and abnormalities in lipid metabolism induced by ovariectomy in a rat model without stimulatory activity on uterus. MATERIALS/METHODS: Ovariectomized (OVX) rats were treated for 6 weeks with 70% ethanol extracts of Hypericum perforatum [HPEs: whole plant (WHPE) and flower and leaves (FLHPE)], ${\beta}$-estradiol-3-benzoate at a dose of $50{\mu}g/kg/day$ (E2) or vehicle (distilled water). RESULTS: As expected, OVX increased body weight gain and adiposity and showed higher food efficacy ratio. OVX also increased the serum cholesterol as well as insulin resistance, while reducing uterus weight and uterine epithelial proliferation rate. HPEs (WHPE and FLHPE) showed estrogen-like effect on body weight gain, adipose tissue weight and food efficacy ratio in OVX rats. HPEs prevented hypercholesterolemia induced by OVX more effectively than E2. E2 increased uterus weight and epithelial proliferation rate in OVX rats, while HPEs maintained them at the level of the sham-operated animals. CONCLUSIONS: Our finding demonstrates that HPEs can be considered as an effective agent to prevent OVX-induced obesity without stimulatory activity on uterus.

• The Korean Journal of Pharmacology
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• v.19 no.1
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• pp.37-60
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• 1983

The uterus receives adrenergic terminals from the mesenteric ganglia and considerably large amount of catecholamines have been shown to be contained in this organ. On the other hand, the activities of epinephrine, norepinephrine or adrenergic nerve on uterine motility is so complicated that many controversial results have been reporter. Recently, a large number of reports concerning the changes of uterine catecholamines content have appeared, but little is known about the role of uterine catecholamines in their activities on uterine motility. The present experiments were undertaken to determine the significance of the intrinsic uterine catecholamines in the physiology of uterus. Female albino rabbits weighing approximately 2 kg were employed in this experiment. uterine strip3 were prepared and suspended in a constant temperature $bath(38^{\circ}C)$ containing 100 ml of Locke's solution aerated with 95% oxygen and 5% carbon dioxide. Spontaneous motility was recorded on a smoked drum with an isotonic lever. The catecholamines concentration of the uterus was determined according to the Procedure described of Shore and Olin (1958). Human uterus obtained from patients was also used to determine the catecholam ines content of myometrium. Followings are summarized results. 1) On the non-pregnant rabbit uterine strips, epinephrine and norepinephrine significantly elevated the tonus and stimulated the spontaneous motility. Pretreatment with dichloroisoproterenol(DCI), an adrenergic beta-receptor blocker, enhanced the stimulatory activity of epinephrine or norepinephrine. On the other hand, pretreatment with dibenamine, an adrenergic alpha-receptor blocker, rendered the uterine muscle to exhibit inhibition after the administration of epinephrine or norepinephrine. Following the treatment with both DCI and dibenamine, epinephrine or norepinephrine produced no appreciable effects on the spontaneous motility of the uterus. These results suggest there exist both alpha and beta-adrenergic receptors in the uterine muscle and the response to epinephrine of the former is predominant over that of latter in the non-pregnant uterus of rabbits. The total catecholamines concentration of the non-pregnant uterus was $351\;m{\mu}g/g$ and the fractional concentrations of epinephrine and norepinephrine were $125\;m{\mu}g/g(35.7%)$ and $226\;m{\mu}g/g$ respectively. It is interesting to note that the catecholamines content of uterus was characterized by a high fractional corcentration of epinephrine relative to norepinephrine. 2) On the pregnant rabbit uterine strips, the effects of epinephrine and norepinephrine varied according to the period of pregnancy. The response to epinephrine of adrenergic beta receptor of uterus increased during pregnancy, and the effect of catecholamine was inhibitory in the early pregnancy but became stimulatory as the pregnancy progressed. This stimulating action on the uterine motility was found to occur through the action of norepinephrine. The uterine catecholamines concentration was markedly reduced during pregnancy. The catecholamines concentration was started to decrease in the early pregnancy, reached the lowest level in the mid-pregnancy and then started to increaae again in the late pregnancy when the total catecholamines content became the highest level of all. This increase of catefholamines in late pregnancy was chiefly due to the increase of norepinephrine. These results suggest that the uterine motility may be related to the catecholamines content, especially norepinephrine content in the uterus. 3) Bilateral oophorectomy of rabbits results in a marked shrink of the uterus in size. The spontaneous motility of the uterine segment of these animals was very weak and irregular. Norepinephrine produced inhibitory effect, whereas epinephrine was stimulatory or inhibitory effect on the uterine segment. The total catecholamines tontent in whole uterus was markedly reduced. The injection of estrogen into the oophorectornized rabbit increased the weight of uterus to approximately three times of that of oophorectornized animal. The apontaneous motility and the response to epinephrine and norepinephrine of the uterine segment were greatly enhanced. Both epinephrine and norepinephrine produced a marked stimulatory effects of the uterine motility. The uterine content of catecholamines, particularly epinephrine, was markedly increased. The injection of progesterone into the oophorectornized rabbit increaeed the weight of uterus to approximately 2.5 times of that of eophorectornized animal. The spontaneous motility of the uterine segment was weak and irregular. Epinephrine produced stimulatory effect at high concentrations but norepinephrine always prcdnced inhibitory effect on the uterine segment. The uterine content of catecholamines, particularly of norepinephrine, was markedly reduced. These results suggested that ovarian hormones play an important role not only on the growth and spontaneous norepinephrine of uterus but also on the catecholamines content and responee to epinephrine and norepinephrine of the uterus. 4) The intraperitoneal injection of reserpine(3 mg/kg) into the non-pregnant, pregnant and oophorectornieed rabbits markedly decreased the uterine content of catecholamines, particularly of the norepinephrine. The stimulatory response to epinephrine and. norepinephrine of the uterine segment of these reserpinized ratbits was markedly reduced whereas the inhibitory response to these catecholamines was enhanced. This finding further support the close relationship between the uterine catecholamines content and uterine response to epineptrire and norepinephrine. 5) In the human uterus, the concentration of epinephrine was actrally greater than that of norepinephrine and it was significantly greater during the proliferative phase of the menstrtal cycle. In the human pregnant uterus, the concentrations of toth epinephrine and ncrefinephrine were markedly reduced and showed about 45 percent rednction after 6-8 weeks of ectopic Pregnancy. At full term ana during labor, the concentrations of epinephrine and norepinephrine at placental sites were less than those found in the non-pregnant group. Of interest was the finding that the norepinephrine concentration of uterus from toxemic patients was two and half times higher than that of lower uterine segment of the nontoxemic pregnant individuals. Also the epinephrine concentraticn was slightly increaeed.

• Proceedings of the Korean Environmental Health Society Conference
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• 2004.06a
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• pp.185-187
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• 2004

The co-administration of BPA and BBP induced slow weight gain compared with single administration in dams. Also, such mixture induced low neonatal body weights in next generation. The dams treated with BPA and BBP showed significant organ weight changes in liver, spleen exposed during lactational periods. But the dams exposed during lactational periods showed significant organ weight changes not only in liver, spleen but also in kidney, uterus and ovary. The F1 female rats exposed during lactation periods showed significant organ weight changes in liver, spleen, ovary. The F1 male rats showed significant organ weight changes in liver, kidney, epididymis, vesicular glands, prostate. However no clear synergistic effects of BPA and BBP could be found. Estrogen receptor ${\alpha}$ expression by BPA and BBP in the uterus(dam, F1 female) and testis(F1 male) were studied. There was no significant different $ER{\alpha}$ expression pattern between control and treated groups. But $ER{\alpha}$ expression were increased in F1 male testis and female uterus. F1 male showed distinct $ER{\alpha}$ expression, especially in the group of lactational combined exposure. Synergistic $ER{\alpha}$ expression was found by combined treatment of BPA and BBP.

• Journal of Nutrition and Health
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• v.12 no.4
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• pp.29-42
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• 1979

In order to observe metabolic effects of an oral conceptive, Norinyle, on female Guinea pig, the changes of ascorbic acid amount and alkaline phosphatase activity in the liver and serum were determined, and histochemical changes of the uterus were observed by microscopic and electronmicroscopic methods by administration of Norinyle with or without ascorbic acid. The results obtained are summerized as follows: 1) The metabolic changes were clearly influenced by the administration of Norinyle alone, but the changes were diminshed by administration of Norinyle with ascorbic acid. 2) The adimnistration of Norinyle influenced to increases the requirment of ascorbic acid in the liver. 3) The uterus weight of the Norinyle administered group was much increased, while the weight was less increased in the group of administered Norinyle with ascorbic acid than the control. 4) The Norinyle administration was brought about an atrophy of endometrium, of uterus especially, functional layer, that the formation of glands were inadequately and the fromation of basal layer and stroma were diminished. 5) An acute infarction on the all layers of the uterus was developed at 9th and 25th days of Norinyle administration and 20th day of Norinyle with ascorbic acid administration. 6) A hypertrophy of stromal and endovascular cells were observed on the groups administered of Norinyle alone(group II ) or Norinyle with ascorbic acid(group IV). 7) It was observed that amount of collagen fiber in the basal and muscular layeres of uterus were diminished under a microscopical observation by the special stained specimen on the Norinyle administered group, but the amount and distribution of reticulin fiber were not changed significantly. 8) The fille structure of outer functional layer of the uterus were significantly changed by administration of Norinyle which were shown irregurarity of nuclear membrane, poor development ana significant expansion of enaoplasmic reticulum, decreases of the amount of ribosome due to slip off, increases of the number of dense bodies, obvious formation of vaccule, an4 decreases the amount of collagen in inner and outer layer of the stroma. 9) The amount of ascorbic acid in the serum did not much changed but the amount in the liver was much decreased by the administration of Norinyle, And the administration of Norinyle with ascorbic acid induced for a significant diminishing on the changes of uterus which might be able to developed by the administration of Norinyle alone.

• Journal of Environmental Health Sciences
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• v.29 no.2
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• pp.16-22
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• 2003

BBP (Butyl benzyl phthalate), a widely used plasticizer. can enter the food and environment as consequence of its manufacture, use, and disposal. BBP was found to be developmental and teratogenic or endocrine disrupting chemical in rats. The effects of BBP were investigated in female rats (P) and second generation (F1) via lactations. Sprague-Dawley were given BBP by oral administration at 0, 5, 10, 100, 1000 mg/kg on day 0 to 21 of lactation period. The results were as follows : At maternal findings, there were some significant changes (p<0.05) in relative organ weight, especially liver and uterus weight by BBP administration. In estrous cycle, high treated group was inclined to be proestrus or estrus compared to control group. BBP indues estrous cycle earlier than the control group. At fetal findings, there were some significant changes in relative liver and spleen weight, especially 100, 1000 mg/kg administered groups. The relative weight of ventral prostate was decreased, so it was represent to dose-response tendency. Parent rats (P) were detected monobenzyl phthalate (MBeP) 3.21~5.81 $\mu\textrm{g}$/ml in 100, 1000 mg/kg dose groups. MBeP of male and female fetuses (F1) were detected at the level of 1.21~2.63 $\mu\textrm{g}$/ml of serum. Male serum concentration oi MBeP was higher than the females'. Estrogen receptor $\alpha$ expression by BBP and bisphenol A in uterus and testis of F1 were studied. The ER$\alpha$ expression were increased in F1 male testis and female uterus. F1 male showed distint ER$\alpha$ expression, especially in the combined exposrue. Synergistic ER$\alpha$ expression was found by combined treatment group of BBP and bisphenol A. From the above results, it could be concluded that the effects of dams and F1 by BBP administration during lactation period were estrogenic, and BBP can transfer to F1 via lactation, and make estrogenic at F1 reproductive organs.

• Korean Journal of Veterinary Research
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• v.13 no.1
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• pp.1-4
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• 1973

This experiment was performed in order to investigate the effect of radioiodine upon the uterus and the ovary of guinea pigs. The animals were injected single dose of 4. 5 mCi of radioiodine per kg of body weight. They were sacrificed on various time intervals; 1, 7, 14, 28, 42 and 56 days after the injection. The results were as follows: 1. In the ovary, the follicle cells and the ova were degenerated with lapse of time after the injection. 2. In the uterus, hyperplasia of the lamina propria of the endometrium and atrophy of the myometrium were observed in accordance with time after the injection.

• Preventive Nutrition and Food Science
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• v.5 no.2
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• pp.75-80
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• 2000

To separate ACE inhibitors from edible plants, spices, and herbs, 285 extracts of 95 sources were screened for ACE inhibitory activity. The extract of Sinapis alba L. had the most potent ACE inhibitory activity. Mustard seeds were crushed homogeneously and extracted with hexane and water successively. Lyophilized water extract was fractionated with $H_2O$:butanol(1:1). The ACE inhibitor was purified from butanol fraction by methanol precipi-tation, gel filtration, HPLC, and FPLC with Superdex peptide HQ 10/30 column. The active fraction has been purified to homogeneity, which was proven by gel filtration using FPLC system. The yield was 0.02%. The com-pound has a molecular weight of about 640. The compound competitively inhibited ACE activity and the $IC_{50}$ value was 79$\mu\textrm{g}$/ml. The purified compound showed uterus contraction activity in isolated rat uterus.