• Journal of Pharmaceutical Investigation
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• v.35 no.3
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• pp.173-177
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• 2005

Addition of 30% propylene glycol was required to maintain sink condition in the evaluation of percutaneous absorption of estradiol and norethindrone acetate. The permeability of estradiol was higher in silicone and SIS adhesives. However, estradiol was crystallized in silicone, SIS, and SBS adhesive matrix. The permeability ratio of estradiol or norethindrone acetate from acrylic pressure sensitive adhesives varied widely depending on the functional group of the acrylic adhesives. PEO grafting to acrylic adhesive seemed to change physicochemical property of acrylic adhesive and increased the permeability of estradiol and norethindrone acetate significantly. On the contrary, highly cross-linked enhancer compatible acrylic adhesive decreased the permeability of both estradiol and norethindrone acetate. $Span^{\circledR}$ 20 provided the highest enhancing effect on the permeability of both estradiol and norethindrone acetate followed by oleic acid and $Crovol^{\circledR}$ EP40. The permeability of the drugs from the developed system was comparable to that from commercial $Combitran^{\circledR}$, although significantly lower amount of estradiol and norethindrone acetate were loaded in the developed system.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.183-189
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• 1991

The present study was performed to elucidate the factors which modulate uterine prostaglandin synthesis during the implantation period in rats, by employing delayed implantation model. Administration of estradiol sharply increased uterine cAMP concentration 4 hrs later during the delayed implantation process. Concentrations of uterine PGE and $PGF_2{\alpha}$ were increased at 12 hrs after the estradiol treatment although an increase in $PGF_2{\alpha}$ was not statistically significant. The concomitant treatment of indomethacin with estradiol significantly suppressed estradiol-induced PGE and $PGF_2{\alpha}$ at 12 hrs, while uterine cAMP concentration was not suppressed. The treatment of dbcAMP without estradiol gradually increased uterine PGE and $PGF_2{\alpha}$ showing the maximum 8 hrs later, suggesting that cAMP minics estradiol effect on uterine prostaglandin synthesis during the implantation process. Furthermore, the pretreatment of theophylline, phosphodiesterase inhibitor, induced significantly greater concentrations of uterine PGE and $PGF_2{\alpha}$, compared with estradiol-only treated group. These results suggest that estradiol stimulates uterine prostaglandin synthesis and this process may be mediated by an elevation of cAMP during the delayed implantation process in rats.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.73-83
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• 1993

In order to examine the effect of ${\beta}-estradiol$ on the cell growth, using a primary rabbit kidney poximal tubule cell culture system. We investigated the effect of ${\beta}-estradiol$ on alpha 1 (IV) collagen and ${\beta}-actin$ mRNA levels from primary rabbit kidney cell cultures, and also the effects of 3 growth factors and ${\beta}-estradiol$ supplementation on the growth of primary rabbit kidney proximal tubule cells in the serum-free medium. 1 nM of ${\beta}-estradiol$ showed a sizable potentiation effect on the growth of the proximal tubule cell in serum-free medium, but higher concentration (> 10 nM) of estradiol indeed inhibited the growth. In the absence of hydrocortisone as a growth supplement in serum-free medium, ${\beta}-estradiol$ caused to potentiate the growth of the cell. In the presence of hydrocortisone, ${\beta}-estradiol$ also potentiated the growth of the proximal tubule cells. According to the Northern analysis, ${\beta}-estradiol$ increased the level of ${\beta}-actin$ mRNA, although mRNA level of the alpha I(IV) collagen was not changed significantly.

• Korean Journal of Veterinary Research
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• v.25 no.2
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• pp.187-195
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• 1985

The Present study has been carried out to elucidate the antiestrogenic effects of tamoxifen in uteri of immature rats. Immature female Sprague-Dawley rats were allocated into 4, groups and injected with $5{\mu}g$ of estradiol-$17{\beta}$, $50{\mu}g$ of tamoxifen, a combination of both or vehicle only subcutaneously three times after an interval of 24 hours respectively. The concentrations, of cytosol estradiol receptor in uterus were measured by DCC method before and 1, 3, 6, 12, 24, 48 and 72 hours after the above treatments and those of nuclear estradiol were measured by protamine exchange method 72 hours and those of nuclear estradiol were measured by protamine exchange method 72 hours after the above treatments. The results obtained were summarized as follows: 1. The binding affinity of tamoxifen to estradiol receptor in uterine cytosol was lower than that of estradiol-$17{\beta}$, accordingly the translocation of estradiol receptor into the nucleus was found to be delayed. 2. Tamoxifen caused the retention of estradiol receptor in nucleus over 24 hours and inhibited the replenishment of the receptor from nucleus to cytosol in uterus.

• The Journal of Korean Physical Therapy
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• v.21 no.2
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• pp.109-116
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• 2009

Purpose: $17\beta$-estradiol is the most active endogenous estrogen, which is related to favorable changes in the plasma lipid profile, to relaxation of the coronary vessels, and to a decrease in platelet aggregation and vascular smooth muscle cell migration. However, although the beneficial effect of estrogens on plasma lipoproteins (ie, lowering low-density lipoprotein and increasing high-density lipoprotein cholesterol) contributes to cardiovascular protection, it does not fully account for the protective effect, particularly in the application of physical therapy, including low frequency electrical stimulation. Methods: The aim of this study was to demonstrate the inhibition of stressors, such as endothelin-1 (ET-1), serotonin (5-hydroxytryptamine, 5-HT), prostaglandin $F2\alpha$ ($PGF2\alpha$), and a protein kinase C (PKC) activator 12-deoxyphorbol 13-isobutyrate (DPB), induced isometric tension by $17\beta$-estradiol in vascular smooth muscle strips, respectively. In addition, the effects of low frequency electrical stimulation at the meridian points (CV-3, -4, Ki-12, SP-6, LR-3, BL-25, -28, -32, -52) on the indirect antihypertensive effect were examined by monitoring the changes in the serum $17\beta$-estradiol concentration in healthy volunteers. Results: Isometric tension analysis showed that the responses of inhibited tension by $17\beta$-estradiol were similar to the same stressors in rat aortic smooth muscle strips. Furthermore, although the continued amplitude modulation (AM) type of electrical stimulation was not increased significantly by electrical stimulation, the current of the frequency modulation (FM) type of low frequency electrical stimulation increased the serum $17\beta$-estradiol concentration in normal volunteers. Conclusion: These results, in part, suggest that $17\beta$-estradiol has the capacity to supress stressor-induced muscle tension, and electrical stimulation, particularly current of the FM type, has a modulatory effect on the sex steroid hormones, particularly $17\beta$-estradiol, in healthy volunteers.

• Korean Journal of Veterinary Research
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• v.37 no.2
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• pp.311-319
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• 1997

The mechanisms of $estradiol-17{\beta}$ regulating growth of both normal and neoplastic cells are not clear until now. In studies using various estrogen-dependent breast cell lines, it is recently known that estrogen controls the cell growth by regulating the expression of growth factors and/or their receptors. In the present study, we investigated the effects of $estradiol-17{\beta}$on cell growth and IGF-I binding sites using primary cultured renal proximal tubule cells. We have obtained results as follows : $Estradiol-17{\beta}(10^{-9})$ has stimulatory effects in cell growth. Cotreatment of $estradiol-17{\beta}(10^{-9}M)$ and $IGF-I(5{\times}10^{-8}M)$ significantly increased the growth of primary rabbit renal proximal tubule cells compared to that of $estradiol-17{\beta}$ or IGF-I alone treated cells. In binding studies, we found that the binding of $^{125}IGF-I$ on cell membranes was incubation time- and temperature-dependent. Incubation at $37^{\circ}C$ results in higher binding of $^{125}IGF-I$ than that of $23^{\circ}C$ or $4^{\circ}C$. Maximum binding was observed at $37^{\circ}C$ between 30 and 60 minutes. The binding of $^{125}IGF-I$ to both control and $estradiol-17{\beta}-treated$ cells was inhibited by unlabelled $IGF-I(10^{-8}{\sim}10^{-12}M)$ in a concentration-dependent manner. However, EGF did not compete for $^{125}IGF-I$ binding at $10^{-8}{\sim}10^{-12}M$. IGF-I binding to the membranes from both control and $estradiol-17{\beta}-treated$ cells was also analyzed. We found that $estradiol-17{\beta}-treated$ cells exhibited higher binding activity for IGF-I. When $estradiol-17{\beta}$ or tamoxifen alone, or $estradiol-17{\beta}$ and tamoxifen cotreated cells were compared, the binding ratio of $^{125}I-IGF-I$ of $estradiol-17{\beta}-treated$ cell was significantly increased but was similar to control in both $estradiol-17{\beta}$ and tamoxifen cotreated cell. These results suggest that $estradiol-17{\beta}$ in part controls cell proliferation by regulating the expression of IGF-I receptors in primary rabbit renal proximal tubule cells.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.191-196
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• 1991

The present study was performed to determine whether estradiol, via cAMP mediation, induces prostaglandin synthesis by modulating phospholipase $A_2$ activity which hydrolyzes phospholipids into arachidonic acids, a precursor for prostaglandin synthesis, during the implantation process in rats. Uterine phospholipase $A_2$ activity was elevated on day 5 of pregnancy when implantation normally occurs in rats. Moreover, phospholipase $A_2$ activity was higher in the implant sites than in the non-implant sites of uterus on day 6. In delayed implantation model, phospholipase $A_2$ activity was increased at 12 hrs after estradiol administration and at 8 hrs after dbcAMP administration. In addition, higher activity of phospholipase $A_2$ was induced by the treatment of estradiol plus theophylline, compared with estradiol-only treated group. The simultaneous treatment of indomethacin with estradiol or dbcAMP did not alter phospholipase $A_2$ activity compared with estradiol or dbcAMP-only treated group although significant suppression was observed in uterine PGE and $PGF_{2{\alpha}}$ concentrations. These results suggest that estradiol or cAMP stimulates uterine phospholipase $A_2$ activity, thereby increasing prostaglandin synthesis during the implantation process in rats.

• Journal of Embryo Transfer
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• v.13 no.3
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• pp.291-300
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• 1998

This study was carried out to elucidate the effect of progesterone, estradiol 17 beta and cholesterol in follicular fluid on sperm chemotaxis for fertilization. By inducing swim-up migration through sucrose layer into bMSS containing progesterone, estradiol 17 beta and/or cholesterol, their effects on sperm migration and sperm movement were examined. And the results obtained were as follows; 1. Progesterone inhibited sperm migration and movement, but significantly attracted capacitated-sperm at the level of 50 $\mu$g/ml. 2. Estradiol 17 beta inhibited sperm migration and movement, but didn＇t significantly inhibit migration of capacitated-sperm at the level of 10$\mu$g/ml. 3. Cholesterol significantly stimulated sperm migration and movement at the level of 50$\mu$g/ml, but didn＇t attact capacitated-sperm. 4. Progesterone and estradiol 17 beta reduced the effect of cholesterol stimulating sperm migration and movement. But estradiol 17 beta and cholesterol didn＇t reduce the effect of progesterone attracting capacitated-sperm. In conclusion, progesterone of 50$\mu$g/ml in bMSS attracted the capacitated-sperm, cholesterol of 50$\mu$g/ml stimulated sperm migration and movement, but estradiol 17 beta of 10$\mu$g/ml didn＇t affect sperm swim-up separation.

• The Korean Journal of Zoology
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• v.19 no.1
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• pp.7-14
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• 1976

The release of ovulatory level of LH from the pituitary gland occurred between 51 and 56 hours after PMS treatment in 24-day old female rats. Estradiol given simultaneously with PMS advanced LH release 24 hours. Injections of estradiol $(2.5\\sim 40\\mu g)$ at 0, 24 and 48 hours failed to increase pituitary LH level by 51 hours after the first injection in ovariectomized rats. However, $5 \\mu g$ estradiol at 0, 24 and 48 hours followed by 1 mg progesterone at 48 hours elevated pituitary L level by 51 hours in ovariectomized rats. These results indicate that advancement of PMS-induced ovulation by estradiol in the previous study occurred by means of inducing premature release of LH and estrogen might synergize with progesterone in the regulation of LH in the pituitary gland.

• Biomedical Science Letters
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• v.14 no.3
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• pp.131-137
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• 2008

Adipogenesis is a complex sequence of events that culminates in the differentiation of fibroblast-like preadipocytes into specialized lipid-filled adipocytes and also involves a cascade of expression of many transcription factors such as peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$ and CCAAT/enhancer-binding proteins (C/EBPs). $PPAR{\gamma}$ and C/EBPs transcriptionally transactivate adipocyte specific genes, including fatty acid transport protein (FAT/CD36) and leptin. To determine whether $17{\beta}$-estradiol modulates $C/EBP{\alpha}$ actions on adipogenesis in high fat diet-fed female ovariectomized (OVX) C57BL/6 mice, mice were treated with $17{\beta}$-estradiol for 7 days and the effects of $17{\beta}$-estradiol on adipose tissue mass and expression of adipocyte specific gene as well as $C/EBP{\alpha}$ were measured. Compared to vehicle-treated OVX control mice, OVX mice treated with $17{\beta}$-estradiol for 7 days had lower adipose tissue weights that were similar to weights in high fat diet-fed sham-operated (Sham) mice. OVX mice showed the increased expression of $C/EBP{\alpha}$ mRNA compared with Sham mice. However, $17{\beta}$-estradiol treatment in OVX mice inhibited OVX induced-$C/EBP{\alpha}$ activation, indicating that $17{\beta}$-estradiol may act as an inhibitor of $C/EBP{\alpha}$ action. Moreover, $17{\beta}$-estradiol decreased mRNA levels of adipocyte marker genes, such as lipoprotein lipase, FAT/CD36 and leptin, to levels in Sham mice. These results suggest that down-regulation of adipogenesis by $17{\beta}$-estradiol may be due to reduced adipose $C/EBP{\alpha}$ activities in female OVX C57BL/6 mice.