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Estradiol-17 beta (E2) and 17 alpha-ethinyl estradiol-17 beta (EE) were compared in terms of their relative capacities to alter growth and developmental patterns of cultured whole embryos during the early stages of organogenesis. Embryos exhibited a notable differential susceptibility to the embryotoxic effects of parents E2 vs EE when these estrogens were added directly to the media at the onset of the culture period. At initial concentrations of 0.1 mM, E2 failed to produce statistically significant effects whereas EE elicited marked embryotoxicity. Inclusion of a P-450-dependent biotransformation system in the culture media resulted in a significant attenuation of the embryotoxic effects of parent E2 vs EE when these estrogens were added directly to the media at the onset of the culture period. At initial concentrations of 0.1 mM, E2 failed to produce statistically embryotoxicity by hepatic S9. The divergent results produced by the two steroids could not be attributed to differences in rates of catecholestrogen generation in the culture medium or by the conceptuses. The results demonstrate definitive dissimilarities between the effects of two steroidal estrogens on developmental parameters and document marked differences in the effects of biotransformation on their embryotoxic potential. The data strongly suggest that the embryotoxicity of these steroids is not mediated via interactions with estrogen receptors. Additionally, the data show that the differential capacity of these two steroids to produce embryotoxic effects is diametrically opposite to earlier reported patterns of their carcinogenic potential in the Syrian hamster kidney. 相似文献
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The combination of polyacrylamide gel electrophoresis and Concanavalin-A-Sepharose affinity chromatography has permitted the isolation on a preparative scale, of four molecular forms of rat alpha1-fetoprotein: a "slow" and a "fast" fraction, each separable into Concanavalin-A-adorbed ("high carbohydrate", i.e. rich in accessible alphaD-Mannosyl and alphaD-Glucosyl residues) and a Concanavalin-A-non adsorbed ("low carbohydrate") fractions. These four iso-alpha-fetoproteins (iso-AFP) bind estradiol-17beta. However, they disclose differences in both their association constants and number of binding sites for this hormone. Very high affinity sites (10(9)) are mainly located on the "slow-low carbohydrate" form. Low affinity, high capacity sites are preferentially located on the "high carbohydrate" form. These results confirm the molecular and functional heterogeneity of rat AFP and suggest that the carbohydrate moiety of the protein may have a role in estrogen-AFP interactions. 相似文献
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The effects of estradiol-17 beta and indomethacin on myometrial gap junction development, plasma estradiol levels and uterine PGF2 alpha content were evaluated in immature and/or ovariectomized, mature rats. High doses of estradiol stimulated the development of gap junctions in the myometrium of animals from both groups. Concomitant injections of estradiol and indomethacin to ovariectomized rats potentiated the estradiol stimulation of gap junctions. Plasma estradiol levels were lower in ovariectomized rats treated with both estradiol and indomethacin than in animals treated with estradiol alone. Indomethacin also enhanced the uptake and retention of 3H-estradiol into uterine tissues. Uterine PGF2 alpha content of ovarectomized rats was stimulated with the initial injection of estradiol but thereafter, the PGF2 alpha content declined with repeated injections to values lower than that observed in controls. Prostaglandin F2 alpha content in tissues from rats treated with estradiol plus indomethacin were also higher than that observed in rats treated with indomethacin alone, however, the values obtained in both groups were significantly lower compared to those from control animals. These results are consistent with the hypothesis that steroid hormones and prostaglandins regulate myometrial gap junction formation. Regulation of myometrial gap junctions by prostaglandins is discussed with respect to a down regulation of the steroid-receptor mechanism and effects on cyclo-oxygenase or lipoxygenase products. 相似文献
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When estradiol-17 beta 17-glucuronide was incubated with male rat liver microsomal preparations with a NADPH-generating system, 2-hydroxyestradiol-17 beta 17-glucuronide was obtained. This 2-hydroxylation was shown to occur without cleavage of the conjugate group. The result clearly indicates that estradiol-17 beta 17-glucuronide could act as substrate for rat liver microsomal 2-hydroxylase. 相似文献
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Distribution, metabolism and excretion of [1-14C]dolichol injected intravenously into rats.
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[1-14C]Dolichol mixed in vitro with rat serum and injected intravenously into rats was rapidly cleared from the circulation in a manner consistent with a two-compartment model. About 80% of the radioactivity recovered from animals killed after 1 day was in the liver, with smaller amounts being found in lung, carcass (internal organs removed), gastrointestinal tract and contents, and spleen. The kidneys, testes and heart contained little radioactivity, and the brain did not appear to take up any [1-14C]dolichol. The half-life for the turnover of radioactivity from [1-14C]dolichol in tissues varied considerably, being 2 days for the lung, 17 for liver and about 50 days for the carcass. After 1 day, and also after 4 and 21 days, most of the radioactivity in all tissues was as [1-14C]dolichol and as [1-14C]dolichyl fatty acyl ester, although a small amount of incorporation of [1-14C]dolichol radioactivity into phospholipids was also observed. Faeces collected over the first 4 days after injection contained 13% of the [1-14C]dolichol dose, but urine and expired air contained only small amounts of radioactivity. Radioactivity in faeces was nearly all as unchanged [1-14C]dolichol and as [1-14C]dolichyl fatty acyl ester. The [1-14C]dolichol remaining in liver after 21 days appeared to be in a pool (possibly lysosomes) where most of it was not subject to excretion. 相似文献
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Regulation of myometrial beta 2-adrenergic receptors by progesterone and estradiol-17 beta in late pregnant rats 总被引:1,自引:0,他引:1
Rat myometrium exhibited a marked decrease in the concentration of beta 2-adrenergic receptors immediately before parturition, i.e., in the last 6 h of pregnancy. This phenomenon continued until the withdrawal of myometrial progesterone (-94% from Day 18 of pregnancy to term) and coincided with the sharp increase (+200%) of the myometrial concentration of estradiol. A linear positive correlation was found (r2 = 0.645) between the concentration of beta 2-adrenergic receptors and the log ratio of myometrial concentration of progesterone/myometrial concentration of estradiol (P/E2), suggesting a modulation of beta 2-adrenergic receptors by steroids. In rats with estrogen-dominated uteri (intact of ovariectomized late pregnant rats injected with estradiol), there was no change either in concentration or affinity of beta 2-adrenergic receptors relative to untreated control pregnant rats. In contrast, rats with progesterone-dominated uteri (intact or ovariectomized late pregnant rats treated with progesterone or ovariectomized rats) have an increased number of beta 2-adrenergic receptors, with a decreased affinity of these receptors compared to untreated control pregnant rats or to estrogen-treated rats. These results suggest that progesterone regulates the number of beta 2-adrenergic receptors in myometrium of late pregnant rats. The mechanisms by which progesterone exerts this regulation remains to be elucidated. 相似文献
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D M Lawson 《Endocrine research communications》1979,6(2):135-148
Repeated intraarterial injections of synthetic thryrotropin releasing hormone (TRH, 1 microgram/rat) increased plasma prolactin levels 4 hours after a single subcutaneous injection of 10 micrograms estradiol-17 beta (E2-17 beta) in rats ovariectomized 1, 2 or 4 weeks and at 2 hours after E2-17 beta injection in rats ovariectomized for 6 weeks. The effect of TRH was still present at 24 but not 48 hours after estradiol treatment. TRH-induced increases in plasma prolactin were similar in groups of rats treated with 10 micrograms E2-17 beta (s.c.) or implanted with 0.5 cm Silastic capsules of crystalline E2-17 beta (s.c.) whereas smaller, yet significant, TRH-induced increases in plasma prolactin were observed in rats injected s.c. with 1.0 microgram E2-17 beta. Single intraarterial injections of TRH at 4 or 8 hours after E2-17 beta treatment induced increases in plasma prolactin similar in magnitude to those observed at the same times after E2-17 beta in rats given repeated TRH injections. No effect of TRH was observed in ovariectomized rats given sesame oil and E2-17 beta treatment did not influence plasma prolactin in rats given saline instead of TRH. Intraarterial administration of serotonin creatinine sulfate (5-HT, 10 mg/kg body weight) induced marked increases in plasma prolactin in rats ovariectomized for 4 weeks which were potentiated at 2 and 6 hours after E2-17 beta (10 micrograms) treatment. The data show that estradiol has a fairly rapid stimulatory effect on plasma levels of prolactin induced by two different secretagogues but the exact site and mechanism of action remain unresolved. 相似文献
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The rate of synthesis of estradiol-17beta by the ovary, and of testosterone by the testis of the newborn rat have been studied in vitro using tissue homogenates. Quantitative estimation of these steroids has shown a peak of activity in the ovary between 8 and 12 days post partum of 63 pg/mg tissue/hr, compared with 6 pg/mg/hr at day 6, and 19 pg/mg/hr at day 14. Testosterone synthesis in the testis is most active on day 1 (3.1 ng/mg/hr), declining steadily to 1.1 ng/mg/hr on day 11. Adult testicular tissue under the same conditions synthesised 0.5 - 1.0 ng testosterone/mg/hr. These results are consistent with other observations which have suggested a transient period of active steroidogenesis immediately after birth in the rat, but the time during which steroid synthesis is elevated has been more clearly defined. The methods described here provide a model system for the study of synthetic steroids and other drugs which may affect the sexual differentiation of the hypothalamus by altering gonadal steroidogenesis. 相似文献
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Preparation and binding of radioactively labeled porcine transforming growth factor type beta 总被引:8,自引:0,他引:8
This report describes the labeling of porcine transforming growth factor type beta (TGF-beta) with 125-iodine. Its binding to NRK cells and three other cell lines has been examined. The data indicate that NRK cells exhibit approximately 10,000 receptors for porcine TGF-beta per cell, with an apparent dissociation constant of 45 pM. The binding of porcine 125I-TGF-beta can be blocked by porcine, murine and human TGF-beta but not by several well characterized growth factors. In all respects examined, the binding observed with porcine 125I-TGF-beta appears to be the same as that observed with human TGF-beta. The findings reported here argue that porcine 125I-TGF-beta can be used to quantitate TGF-beta receptors on a wide range of mammalian cells. 相似文献
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Peripheral levels of progesterone and estradiol 17beta were quantified in 27 cycling cows following administration of a single Hydron ear implant (G. D. Searle and Co.) containing 2, 4 or 6 mg norgestomet or controls which received no implant. Implants were inserted subcutaneously in the ear on day 15 of the estrous cycle (day of estrus = day 0) and removed 9 days later. The 4 mg (seven of seven cows) and 6 mg (six of six cows) implants suppressed estrus; however, three of eight cows in the 2 mg group exhibited estrus prior to implant removal. The 6 mg implant group had a significantly longer interval from implant removal to estrus than either the 2 or 4 mg group. Failure to detect differences in the rate at which progesterone declined indicated norgestomet treatment did not affect normal corpus luteum regression. Estradiol levels rose at a similar rate approaching estrus in all treatments. There was no indication of increased endogenous estradiol levels due to norgestomet treatment. 相似文献
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E2-17β and E2-17α give substantially similar yields of 3-methyl ether and dimethyl ether when methylated by Brown's procedure. 相似文献
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A series of 3 experiments were conducted to evaluate superovulatory response following exogenously controlled follicular wave emergence in cattle. In Experiment 1 the hypothesis was tested that treatments with progestogen plus estradiol-17beta (E-17beta) would result in the emergence of a wave of ovarian follicles that are as responsive to exogenous gonadotropins as those of a spontaneous follicular wave. Beef cows and heifers either received a progestogen ear implant on Day 0 (ovulation) plus 5 mg im E-17beta on Day 1 and were superstimulated on Day 5, or did not receive implants but were superstimulated on Day 8 (expected day of emergence of the second follicular wave). The cattle received 400 mg NIH-FSH-P1 of Folltropin-V, given in a single subcutaneous injection or twice daily as intramuscular injections over 4 d. No significant differences were detected between the 2 groups in the number of corpora lutea (CL), ova/embryos collected, fertilized ova and transferable embryos. In Experiment 2 superstimulatory responses to a single subcutaneous injection of Folltropin-V were compared between heifers in which follicle wave emergence was synchronized with progestogen plus E-17beta at unknown stages of the estrous cycle with those treated following a conventional method of superstimulation at middiestrus. Superstimulation 4 d after E-17beta treatment in heifers with progestogen implants resulted in a similar superovulatory response and higher fertilization rates than those initiated 8 to 12 d after estrus. In Experiment 3 the ovarian response to a single- versus multiple-injection superstimulatory treatment protocol was compared in heifers given progestogen plus E-17beta to induce synchronous wave emergence. The number of CL, ova/embryos collected, fertilized ova and viable embryos were not different between groups. Superstimulatory treatments initiated 4 d after E-17beta treatment of cattle with progestogen implants resulted in comparable ovulatory responses to treatments initiated at the time of spontaneous wave emergence or during middiestrus. Synchronizing wave emergence in a group of randomly cycling cattle obviated the need of estrus detection and synchronization prior to superstimulation. 相似文献
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High- and low-affinity prostaglandin E2 (PGE2) binding sites were found on day 15 after estrus in the endometrium of cycling (Cy) and pregnant (Pr) gilts as well as gilts treated with intra-uterine Silastic beads containing estradiol-17 beta (E2) alone or in combination with PGE2 (E and PG gilts respectively) and inserted into the uterine lumen on day 10 of the cycle. The average apparent dissociation constants (Kd) and binding site concentrations (Bmax) for the high- and low-affinity sites were respectively (mean +/- SEM): 8.4 +/- 0.7 pM and 3.28 +/- 0.38 fmol/mg of protein and 5.3 +/- 0.8 nM and 71 +/- 9 fmol/mg of protein. Samples collected along the meso- and antimesometrial aspects did not differ (P greater than 0.05), although the low-affinity Bmax was higher on the antimesometrial aspect for Pr and Cy gilts only. No difference in Kd (P greater than 0.10) was found between treatments for high-affinity binding sites. For the low-affinity binding sites, Kd was higher for Pr compared to PG and E but not to Cy gilts (P less than 0.05). The high-affinity Bmax was higher (P less than 0.05) for PG, followed by E, Pr and Cy gilts (respectively: 5.50 +/- 0.26; 4.19 +/- 0.46; 1.78 +/- 0.40; 1.64 +/- 0.23 fmol/mg of protein), although Pr and Cy gilts were not different (P greater than 0.05). These results suggest that the localized presence of conceptuses in the uterus in early pregnancy does not markedly affect PGE binding sites but that intrauterine applications of Silastic beads containing E2 and PGE2 increase high-affinity Bmax and decrease low-affinity Kd. 相似文献