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1.
《Journal of steroid biochemistry》1984,20(4):1047-1055
The biological responses of estriol (E3) and of estriol-3-sulfate (Ea3-S) in the fetal and newborn uteri of guinea pig were studied. After a treatment of E3 (1 mg/kg/day) or E3-S (1.4 mg/kg/day) to pregnant guinea pigs (49–60 days of gestation) for 6 days, both estrogens provoke a significant uterotrophic effect in the fetal uterus which increases in weight 1.8–2.5 times in relation to the non-treated animals. The stimulation of progesterone receptor (PR) is also very intense, 7–12 times in relation to the control animals.In another series of experiments newborn guinea pigs (2-day old) were treated with 100μg/animal of E3 or 140 μg/animal of E3-S for a short (2 days) or a long (12 days) period. Concerning the uterotrophic effect, the weight of the uterus increases 1.8–2.5 times (in relation to the non-treated animals) after a 2-day treatment and the effect continues to increase up to 4–5 times in the 12-day treated animals. In opposition to the fetal uterus, the effect on PR provoked by E3 or E3-S is very limited (only an increase of 1 time in relation to the non-treated animals); the effect is even less intense after the 12-day treatment. Histological studies show an intense hypertrophic effect particularly in the epithelium of the endometrium in the fetal and newborn uteri for both E3 and E3-S. In the newborns the effect is also intense on the epithelium of the uterine gland.It is concluded that: (1) Estriol and estriol sulfate are very active and with similar intensity on the uterine weight before and after birth; (2) The stimulatory effect on PR decreases very significantly after birth and after a long treatment; (3) E3S can act as a potent hormonal precursor. 相似文献
2.
《Journal of receptor and signal transduction research》2013,33(3):439-457
AbstractThe uterus of the guinea pig fetus has been shown to respond to estradiol treatment by an increase in uterine wet weight and a stimulation of the progesterone receptor protein. A study of the kinetics of these two parameters of estrogen response in the fetal uterus was undertaken in order to correlate these responses with changes in the estrogen receptor. Administration of estradiol to pregnant guinea pigs (1 mg/kg/body weight) leads to a rapid stimulation of the progesterone receptor by 6h after treatment which reaches maximal values by 15.5h, which are increased 7-fold in estradiol-primed guinea pigs above values in untreated animals. The estradiol receptor undergoes rapid translocation from the cytosol into the nucleus by 1h after hormone treatment and is retained in the nucleus for at least 6h. At the same time, there is a 50% decrease in the total occupied and available estradiol receptor concentration at 6h after treatment. Estradiol treatment also provokes an increase in wet weight of the fetal uterus which is significantly greater after 3 consecutive days of treatment (171% ± 24 (S.D.) above wet weights of untreated uteri which were considered as 100%) than after only 1 day (121% ± 25 (S.D.)). These estrogen responses were found to be of long duration since uterine wet weights and progesterone receptor concentrations remained well above control values even 5 days after a single treatment with estradiol. In conclusion, the fetal uterus responds to estradiol treatment by a slow increase in wet weight and a rapid stimulation of the progesterone receptor protein with a concomitant loss in estradiol receptor concentration. 相似文献
3.
《Journal of steroid biochemistry》1984,20(4):1033-1037
The biological effects of estriol (E3) have been studied in three estrogen targets, namely, the rat uterus in vivo and in vitro, in primary human endometrial cell cultures and in MCF-7 human breast cancer cells in culture. Studies on the temporal relationships between estrogen receptor binding and biological responses in the uterus using estriol and several more long-acting estriol derivatives, namely, 17α-ethynyl estriol, estriol-3-cyclopentyl ether, and 17α-ethynyl estriol-3-cyclopentyl ether, indicate that estriol is a short-acting compound with a brief duration of action. Estriol is a poor stimulator of uterine growth and plasminogen activator activity in vivo. Chemical modifications of the estriol molecule produce long-acting derivatives that result in a prolonged input of hormone receptor complexes into the nucleus and a prolonged and marked stimulation of uterine growth. In human endometrial cells in primary tissue culture, E3 has 12% the affinity of estradiol (E2) for cytosol estrogen receptor and it is quite effective yet slightly less potent than estradiol in stimulation of progesterone receptor synthesis. Low concentrations of E3(10−10 M) stimulate growth of MCF-7 cells in vitro and dose-response curves show E3 to be only slightly less effective than E2. In these endometrial and breast cancer cell systems in vitro, there is no metabolism of E3 while E2 is metabolized to estrone.Hence, estriol is an effective estrogen in vitro. In vivo, it is short-acting, but it can be made a full estrogen agonist when given at a sufficiently high concentration or in a chemically modified form which prolongs its activity by enabling effective concentrations of the compound to be maintained in the blood and in target tissues. 相似文献
4.
Guinea pig fetuses were treated with progesterone for 7 days before placing fetal uteri in organ culture to see if progesterone pre-treatment of fetuses in utero would permanently inhibit the spontaneous rise in progesterone receptor which occurs in organ culture. The data show that: the basal level of progesterone receptor in fetal uteri was not affected by the progesterone treatment and progesterone receptor concentrations in vitro were also not inhibited. When guinea pig fetuses were treated sequentially with progesterone and estradiol, estradiol failed to provoke an uterotrophic effect but it retained its ability to stimulate progesterone receptor concentrations. 相似文献
5.
L S Persianinov S V Sturchak E G Bobrova R N Shchedrina N D Fanchenko 《Biulleten' eksperimental'no? biologii i meditsiny》1975,79(5):93-96
It was demonstrated on the uteri of women and guinea pigs that estriol (in vitro) possessed a marked affinity to the estradiol-binding system of human and guinea pig uteri; the activity of steroid-receptor interaction of estriol in vitro constituted 9.4% for guinea pigs and 17% for man in relation to the estradiol activity. Administration of estriol to guinea pigs in vivo in a dose of 0.25-0.5 mg led to a sharp reduction of the estradiol-binding capacity of the receptor system of the uterus. It is supposed that there existed a competitive relationship between estradiol and estriol for binding with the active centres of the receptor proteins of the uterus. 相似文献
6.
Brain uptake and metabolism of estradiol benzoate and estrous behavior in ovariectomized guinea pigs
Groups of spayed guinea pigs were injected sc with tritiated estradiol benzoate in oil and killed at intervals varying from 12 to 120 hr later. The quantities of radioactivity with the mobility of estrone (E1), estradiol-17β (E2), and estriol (E3) were estimated in plasma, hypothalamus, cortex, and cerebellum. Radiometabolites extracted from the hypothalamus and the cortex were identified by derivative formation and by isotope dilution techniques. The hypothalamus contained larger quantities of E2 than any of the other tissues studied. The same pattern of uptake and decay of radioactivity was observed in all tissues. Concentration of total radioactivity was greatest 12 hr after injection and declined fairly regularly to minimal value at 120 hr. Unlike the hypothalamus and the cerebellum, in the cortex a large proportion of the radioactivity was present as E1. 3H-estradiol benzoate was metabolized to 3H-estradiol by blood in vitro suggesting that the esterified form of the hormone is long lasting because of its slow release from the site of injection rather than its long half-life in the blood.Additional groups of spayed guinea pigs were tested for lordosis in response to fingering after injection of estradiol benzoate followed by progesterone at intervals varying from 12 to 120 hr. The expression of lordosis varied in a complex manner as a function of the interval between the injection of estradiol benzoate and progesterone. Maximum measures of lordosis were obtained when the interval between injections was 36 hr. The relation between behavior and the neural uptake of estrogens suggests that both the duration of estrogen action and the concentration of estrogens at the time the behavior is being displayed determine the character of the response. 相似文献
7.
《Journal of steroid biochemistry》1982,16(4):363-369
This report describes the measurement of estrogen and progesterone receptors in cytosols and nuclear fractions from endocervical tissue components. Unoccupied cytosol estrogen receptor levels as determined by Scatchard analysis of [3H]-estradiol binding data indicated a single class of high affinity binding sites for the epithelial-stromal complex (KD = 0.74 × 10−9 M). Binding was specific for estrogen (estradiol > estriol > estrone) and unaffected by desoxycorticosterone, dihydrotesterone and progesterone. Assays for total estrogen receptor verified that 71.6 ± 5.3% of this 8S estrogen receptor is in the epithelial-stromal complex while the remaining approximately 28% is localized in the stroma and fibromuscular wall, with the cells of the complex containing the highest receptor concentration. In 5-day pseudopregnant and ovariectomized rabbits compared to estrous rabbits there was a 50% decrease in the cytosol estrogen receptor in the epithelial-stromal complex and a 30% decrease in the concentration of nuclear receptor. Cytosol and nuclear progesterone receptors were measured as an indicator of estrogen action in the rabbit endocervix. Cytosol progesterone receptor concentrations (fmol/mg DNA) in 5-day pseudopregnant and ovariectomized animals were reduced to approximately 35% of the concentration in estrous animals. Nuclear progesterone receptor concentrations decreased 65% in 5-day pseudopregnant and 90% in ovariectomized animals suggesting decreased receptor synthesis. Collectively these data support the concept that the rabbit endocervix may be directly regulated by estrogens. 相似文献
8.
Cells from the uterus of the guinea pig fetus have been grown as a monolayer culture in serum-containing medium. Cells from the first subculture showed high concentrations of progesterone receptor (PR; 9.3-13.8 pmol/mg DNA) even after 9 days in medium containing charcoal-treated serum and estradiol did not induce any further increase. The antiestrogens, tamoxifen and monohydroxytamoxifen, both had an inhibitory effect which could be overcome by estradiol. The progestins, progesterone and R5020, as well as the antiprogestin, RU38486, also decreased the PR concentration. Estrogen receptor (ER) levels did not vary with the compounds tested but were found to be low compared to concentrations found in the fetal guinea pig uterus at 55-65 days of gestation. None of the compounds tested had any effect on the growth of the fetal uterine cells so that the modulation of PR concentrations was dissociated from the regulation of cell growth. It is concluded that estrogens are necessary but not sufficient factors in the control of PR levels in fetal uterine cells. The establishment of a culture system for separate types of fetal uterine cells will permit us to study in vitro the factors involved in the growth effects of estrogens and the control of PR synthesis. 相似文献
9.
《Journal of steroid biochemistry》1984,20(1):121-128
The antagonistic effects of progesterone and of the anti-estrogens, tamoxifen and nafoxidine, to estrogen responses were studied in the target tissues of fetal and newborn guinea pigs. In the fetal uterus, progesterone inhibits the stimulatory effect provoked by estradiol on uterine growth, on progesterone receptor and on the acetylation of nuclear histones. Progesterone also blocks the synthesis of new progesterone receptor protein in organ culture. Tamoxifen or nafoxidine (1 or 10mg/kg/day injected to the mother for 3 days) provoke a uterotrophic effect similar to that of estradiol (1 mg/kg/day injected to the mother for 3 days) but these anti-estrogens have a limited effect on the progesterone receptor. Tamoxifen given together with estradiol antagonizes the effect of the estrogen on the acetylation of histones but the anti-estrogens do not block the effect of estradiol on uterine growth. Histological studies show that both estradiol and tamoxifen provoke a dramatic hypertrophie and hyperplastic effect particularly in the uterine epithelium.In the newborn uterus (6-day old), tamoxifen (s.c. injection of 0.6μg/g body weight) and estradiol (injection of 30 ng/g body weight) provoke a similar uterotrophic effect and both have a limited effect on the progesterone receptor.In the fetal thymus estradiol provokes a selective decrease in the larger and actively proliferating lymphoid cells of the cortical zone. Tamoxifen has a similar effect but to a much lesser extent than estradiol. On the other hand, tamoxifen antagonizes the effect of estradiol on this fetal tissue.It is concluded that during fetal life progesterone antagonizes the effect of estradiol but tamoxifen can act as an agonist or an antagonist of estrogen action which is a function of the type of response or organ considered. 相似文献
10.
Jorge R. Pasqualini Chantal Cosquer-Clavreul Chantal Gelly 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1983,739(1):137-140
The effect of estradiol, progesterone, tamoxifen, estradiol + progesterone or estradiol + tamoxifen on the [3H]acetylation of histones in the fetal uterus of guinea pig was studied. The fetuses were injected subcutaneously ‘in situ’ with the hormones or alone. In 10 min, estradiol stimulated the acetylation of histone 10–12-times with respect to the control animals. Progesterone and tamoxifen blocked this effect. It is suggested that histone acetylation is an early step induced by estrogen action during intrauterine life and that progesterone and tamoxifen suppress this mechanism very effectively. 相似文献
11.
J R Pasqualini C Sumida N A Giambiagi B L Nguyen 《Journal of steroid biochemistry》1987,27(4-6):883-889
The actions and biological responses of anti-estrogens are a function of: the experimental conditions, the parameters, the organ and the animal species considered. Target tissues for estrogens in the guinea-pig during the perinatal period are interesting models to explore the action of anti-estrogens. The summary of the data indicates: (1) In the fetal uterus of guinea-pig in in vivo experiments (after injection to the maternal compartment) tamoxifen acts as a real agonist concerning growth, as a partial agonist concerning the stimulation of the progesterone receptor. (2) In in vitro experiments (in organ culture of fetal uterus or in isolated cells) anti-estrogens (tamoxifen or 4-hydroxy-tamoxifen) act as antagonists and also inhibit the effects provoked by estrogens. (3) In the uterus and vagina of newborn guinea-pigs, tamoxifen and its derivatives: 4-hydroxytamoxifen and N-desmethyltamoxifen act as real agonists concerning the uterotrophic and vaginotrophic effects, and also stimulate the amount of DNA per organ, but concerning the progesterone receptor in the uterus, in the short treatment anti-estrogens act as partial agonists but they have no effect in the long treatment. In the vagina in the short treatment anti-estrogens provoke no significant effects, but in the long treatment they are full agonists. In neither of the two biological responses studied (growth and progesterone receptor) does tamoxifen and its derivatives block the action of estradiol. (4) The use of a monoclonal antibody to the estrogen receptor revealed quantitative differences in the activation of the estrogen receptor when bound to estradiol or tamoxifen. This observation was in agreement with the lesser extent of binding to DNA-cellulose of the tamoxifen-estrogen receptor complex as compared with the estradiol-estrogen receptor complex. This fact suggests an impaired activation of the estrogen receptor induced by tamoxifen which might be related to the different biological responses provoked by estrogens and anti-estrogens. 相似文献
12.
《Journal of steroid biochemistry》1984,20(4):1021-1026
The effect of estriol on the positive cooperativity of [3H]estradiol binding to the partially purified calf uterine estrogen receptor was investigated using the kinetic analysis of Sasson and Notides (J. biol. Chem. 257 1982, 11540). The receptor was titrated with variable concentrations of [3H]estradiol with or without estriol; the estriol was maintained in a constant molar ratio to the [3H]estradiol concentration. A 4-fold molar excess of estriol above the [3H]estradiol concentrations inhibited the receptor's cooperative [3H]estradiol binding. In the absence of estriol, the [3H]estradiol receptor interaction was highly cooperative, the Scatchard plot was convex and the Hill coefficient was 1.61 ± 0.02a. In the presence of sufficient estriol to reduce the maximally bound [3H]estradiol to 77%, the Scatchard plot was linear and the Hill coefficient was 1.04 ± 0.04. The inhibition of the cooperative [3H]estradiol binding by estriol was not due to isotope dilution of the specifically bound [3H]estradiol by the unlabeled estriol.These data demonstrate that the cooperative binding of 3H]estradiol by the receptor that is characteristic of the equilibrium between the two states of the receptor (active and nonactive) is eliminated by the presence of estriol. This finding is consistent with the agonist/antagonist activity of estriol observed in vivo. 相似文献
13.
《Journal of steroid biochemistry》1984,20(4):975-979
Published results from in vivo experiments carried out in Rhesus monkeys and from in vitro perfusions of human term placentas have indicated that placental estradiol (E2) is preferentially released towards the mother whereas estrone (E1) is about evenly distributed between fetal and maternal circulation.In order to examine the distribution of estriol, relative to that of E1 and E2, we have now prepared [3H]16-hydroxyandrostenedione by incubation of [6,7-3H]androstenedione with Streptomyces roseochromogenus and perfused placental cotyledons with mixtures of these two labeled precursors. Measurement of the concentrations of tritiated E1, E2 and E3 in the maternal and fetal perfusates, flowing at approx 10 and 5 ml/min, respectively, indicated that the distribution of E3 is different from that of E2 and resembles the distribution of E1.The simple perfusion system being used shows differences in the distribution of various estrogens between fetal and maternal perfusates which may reflect the in vivo situation and offers the opportunity for experimental examination of various explanations for these differences, e.g. existence of specific carrier systems in the syncytial membranes, specific binding of the estrogens to secreted placental proteins, and actions of placental and decidual 17β-hydroxysteroid dehydrogenases. 相似文献
14.
Ovariectomized adult guinea pigs were treated with a regimen of estradiol benzoate (0.2 μg/animal estradiol benzoate at hr 0 and 19) that was shown to be minimally effective for the induction of lordosis. They were then treated with 10, 20, or 80 mg of enclomiphene, 5, 20, 40, or 100 μg of estradiol, or testosterone, cortisol, estrone, estriol, diethylstilbestrol, catechol estradiol, or catechol estrone (all at a dose equivalent to 5 μg of estradiol) at hr 28. At hr 39 all females were given 0.5 mg progesterone, and subsequently tested for lordosis behavior. Of the various agents injected at hr 28 only estradiol (at all doses given), estrone, estriol, and diethylstilbestrol were effective in supporting display of lordosis behavior. The results indicate that the antiestrogen enclomiphene, the catechol estrogens, and at least some C19 and C21 steroids are weaker than E2 or ineffective in facilitating lordosis behavior when given late in the priming period. Because previous work had shown that enclomiphene has partial estrogenic effects on lordosis behavior when administered early in the priming period (i.e., at hr 0, 19), it is suggested the early and late phases of the priming process induced by E2 entail qualitatively different neural processes. 相似文献
15.
Although mercuric chloride has toxicity on reproductive system, it is uncertain if such toxicity is induced by estrogen-like
effect. To study whether mercuric chloride has the estrogen-like effect and its relevant mechanism, proliferation assay of
MCF-7 human breast cancer cells, uterotrophic assay, peroxidase activity assay and estrogen receptor competitive binding assay
were conducted to screen the estrogen-like effect of mercuric chloride. The MCF-7 cells proliferated in the stimulation of
mercuric chloride and got to the peak at 10−7 mol/l concentration. And this proliferation could be completely blocked by estrogenic antagonist ICI182.780. In addition,
mercuric chloride could increase the weight of uterus of ovariectomized SD rats and the peroxidase activity of uterus complying
with dose-effect relationship. However, mercuric chloride could not affect the binding of estradiol (E2) to estrogen receptor (ER). So mercuric chloride exhibits the estrogen-like effect through binding and activating ER rather
than bind to ER by competing with E2. 相似文献
16.
The translocation of progesterone receptor from the cytosol into the nucleus was studied under "in vivo" and "in vitro" conditions in the uteri of guinea pig fetuses exposed to progesterone or a synthetic progestin, R5020. Progesterone treatment of estrogen-primed fetuses leads to a rapid (before 1h) transfer of cytosol progesterone receptor into the nucleus which is, however, short-lived (less than 3h). A rapid decrease in the retention of the estrogen receptor in the nucleus also occurs. In the "in vitro" incubations of whole fetal uteri, translocation of progesterone receptor is temperature-dependent and specific for progesterone and R5020; estradiol and cortisol have no effect. Putative progesterone receptors can also be induced in explants of fetal guinea pig uteri in organ culture which translocate from the cytosol into the nucleus under the same "in vitro" conditions as in whole uteri. Fetal uterine progesterone receptor, either stimulated "in vivo" by estrogen-priming or induced in organ culture, translocates from the cytosol into the nucleus and this process seems to be accompanied by a decrease in retention of the estrogen receptor in the nucleus which appears to be the mechanism by which progesterone antagonises estrogen action in fetal guinea pig uterus. 相似文献
17.
《Journal of steroid biochemistry》1984,20(4):1027-1032
The interaction of [3H]estriol with the partially purified estrogen receptor from calf uterus shows positive cooperativity that is dependent upon receptor concentration and temperature. At a receptor concentration of 1 nM and 25°C the [3H]estriol-receptor cooperativity was low, the Hill coefficient (nH) was 1.03 ± 0.02; however, with increasing receptor concentrations the receptor's cooperativity increased until at approximately intracellular receptor concentration (20 nM) the nH = 1.20 ± 0.04. At 0°C and a receptor concentration of 10 nM the [3H]estriol-receptor interaction was highly cooperative, the Scatchard plot was convex and nH = 1.58 ±0.04 while at 30°C the Scatchard plot approached linearity and nH = 1.03 ± 0.02. In comparison, [3H]estradiol was capable of inducing, at 0 or 30°C and at a receptor concentration of 1 nM or greater, maximal receptor cooperativity, nH = 1.63.These data demonstrate: (a) the receptor's conformation and binding mechanism change in a specific manner with temperature, so that receptor analysis at 0°C does not necessarily reflect the receptor's properties at biologically relevant temperatures; (b) the dependence of the receptor's cooperativity on receptor concentration, which suggests interaction between dissociable subunits; and (c) the lower cooperativity induced by estriol, in comparison with estradiol, which indicates estriol is less efficient in shifting the receptor toward a higher affinity or the activated state of the receptor. 相似文献
18.
19.
《Journal of steroid biochemistry》1984,20(4):1039-1046
The cytosolic estrogen receptor (calf uterus) bound to estradiol (E2) at 0°C changes from a state with fast into a state with slow E2 dissociation rates when placed at 28°C. This temperature accelerated transition in receptor affinity for its ligand takes place within 10 min at 28°C. Similarly, receptor bound to estriol (E3) at 0°C changes, when heated, from a state with fast into a state with slow E3 dissociation. The main difference between RE2 and RE3 was that E3 dissociates from unheated 8S RE3 and heat-transformed 5S RE3 at a much faster rate than E2 from RE2;In the mature ovariectomized rat a slow dissociating 5S receptor estrogen complex is found in nuclei 1 h after injection of [3H]E2 or [3H]E3. In vitro dissociation of these 2 estrogens from this nuclear bound receptor formed in vivo takes place at rates similar to those from heat-transformed cytosolic RE2 or RE3 complexes.Addition of pyridoxal 5'-phosphate (PLP) to the slow-dissociating heat-transformed 5S estrogen receptor complexes causes rapid dissociation of E2 or E3; this effect is dose-dependent and is not due to disruption of 5S dimers, since after PLP addition RE2; and RE3 sediment unchanged as 5S dimers.The presence of a large excess of non-radioactive 4S RE3 does not interfere with the temperature induced rapid transition of 4S R[3H]E2 complexes from the state with fast into a state with slow E2 dissociation kinetics.A model is presented to explain the temperature induced biphasic estrogen dissociation from the receptor. It is proposed that the low affinity 4S RE2 monomer undergoes a temperature and estrogen dependent conformation change, such that the ligand is “locked” into the receptor's binding site. This conformational change results in the formation of a high affinity 4S monomer from which estrogen dissociates at a slower rate. This reaction is independent from subsequent 4S to 5S dimerization (transformation). The different rates of ligand dissociation from the low and high affinity 4S receptors reflect the different interactions (hydrophobic and hydrogen bonding) of E2 and E3 with the estrogen binding domain. 相似文献
20.
Hormonal control of implantation in guinea pigs 总被引:1,自引:0,他引:1
In the guinea pig, for which implantation is supposedly progesterone-dependent, actual hormonal requirements were assessed by measuring the levels of circulating estradiol and progesterone and correlating them with their content in the ovaries and uterus, and uterine concentrations of their receptors prior to, during, and immediately after implantation. Ovarian and uterine content and plasma levels of estradiol and progesterone, as well as uterine cytosolic receptors of these two hormones, were high at proestrus. Up to day 3 of pregnancy, estradiol remained high in peripheral plasma, ovarian and uterine tissues, but reached low levels at the time of implantation. The levels of progesterone showed a gradual increase in plasma and ovaries till the time of implantation, with the embryonic site of the uterus accumulating more of progesterone compared to estradiol. As pregnancy progressed, a gradual translocation of cytosolic to nuclear receptors occurred, both with estradiol and progesterone receptors. Comparing the receptor values for estradiol at each uterine site showed no significant alterations between embryonic and interembryonic cytosolic receptors. While significantly high levels of nuclear estradiol receptor were found at the inter-embryonic site on day 9 of pregnancy, the cytosolic and nuclear progesterone receptor concentrations were greater at the embryonic site on the same day. These findings demonstrated that the uterus is adequately exposed to estradiol and progesterone prior to ovulation and again in early pregnancy (day 1-3), thus facilitating implantation in the guinea pig (on days 7-8). 相似文献