首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 31 毫秒
1.
2.
The substituted triphenylethylene antiestrogen clomiphene (CLO) prevents cancellous bone loss in ovariectomized (OVX'd) rats. However, CLO is a mixture of two stereoisomers, enclomiphene (ENC) and zuclomiphene (ZUC), which have distinctly different activities on reproductive tissues and tumor cells. The purpose of the present dose response study was to determine the effects of ENC and ZUC on nonreproductive estrogen target tissues. These studies were performed in 7-month-old female rats with moderate cancellous osteopenia that was established by ovariectomizing rats 1 month before initiating treatment. OVX resulted in increases in body weight, serum cholesterol, endocortical resorption, and indices of cancellous bone turnover, as well as decreases in uterine weight, uterine epithelial cell height, bone mineral density, bone strength, and cancellous bone area. Estrogen treatment for 3 months restored body weight, uterine histology, dynamic bone measurements, and osteoblast and osteoclast surfaces in OVX'd rats to the levels found in the age-matched sham-operated rats. In contrast, estrogen only partially restored cancellous bone volume and uterine weight, and it reduced serum cholesterol to subnormal values. CLO was a weak estrogen agonist on uterine measurements and a much more potent agonist on body weight, serum cholesterol, and dynamic bone measurements. CLO increased trabecular thickness in osteopenic rats and was the most effective treatment in improving cancellous bone volume and architecture. ZUC was a potent estrogen agonist on all tissues investigated and had dose-dependent effects. In contrast, ENC had dose-dependent effects on most measurements similar to CLO and decreased the uterotrophic effects of ZUC. It is concluded that ENC antagonizes the estrogenic effects of ZUC on the uterus but that the beneficial effects of CLO on nonreproductive tissues in OVX'd rats is conferred by both isomers. Furthermore, the combined actions of the two isomers on bone volume and architecture were more beneficial than either isomer given alone.  相似文献   

3.
Raloxifene is a selective estrogen receptor modulator that in experimental animals acts as an estrogen receptor antagonist in breast and endometrium but as an estrogen receptor agonist in the skeletal and cardiovascular systems. We conducted a 1-year prospective, randomized, double-blind trial in 143 postmenopausal osteoporotic women (mean +/- SD age, 68.4+/-5.0 years) with at least one prevalent vertebral fractures and low bone mineral density (BMD), comparing groups receiving raloxifene at 60 mg/day (RLX60) or 120 mg/day (RLX120) and a control group receiving supplements of 750 mg/day of calcium and 400 IU/day of vitamin D. There were no differences among groups in the occurrence of uterine bleeding, thrombophlebitis, breast abnormalities, or increased endometrial thickness (assessed by ultrasonography). As compared with controls, the changes in values over 1 year for RLX60 and RLX120, respectively, were significant for serum bone alkaline phosphatase (-14.9%, -8.87%), serum osteocalcin (-20.7%, -17.0%), and urinary C-telopeptide fragment of type I collagen/creatinine (-24.9%, -30.8%), markers of bone turnover; for serum total cholesterol (-7.0% for RLX60) and low density lipoprotein cholesterol (LDL) (-11.4% for RLX60) and for the LDL/HDL cholesterol ratio (-13.2%, -8.3%). BMD increased significantly in the total hip (1.66% for RLX60) and ultradistal radius (2.92%, 2.50%). There were nonsignificant trends toward increases over controls in BMD for lumbar spine, total body, and total hip (for RLX120). Using a >15% cutoff definition, raloxifene had no effect on incident fractures, but using a >30% cutoff, there was a dose-related reduction (p = 0.047). We conclude that raloxifene therapy is well tolerated, reduces serum lipids, and does not stimulate the uterus or breasts. It has beneficial effects on bone, although, under the conditions of this study, these appear to be of a smaller magnitude than have been reported with estrogen therapy.  相似文献   

4.
The crystallization of the ligand-binding domain (LBD) of the estrogen receptor (ER) with 17beta-estradiol and raloxifene [A. M. Brzozowski et al., Nature (Lond.), 389: 753-758, 1997] now provides a molecular basis for the biological activity of complexes as either agonists or antagonists. It is well established that the critical structural feature of antiestrogens is a correctly positioned alkylaminoethoxy side chain. The X-ray crystallography clearly shows that the alkylaminoethoxy side chain of raloxifene causes a specific and inappropriate molecular perturbation of the LBD and that the nitrogen in the side chain must hydrogen bond with aspartate 351 in the LBD of ER. We previously identified and characterized a naturally occurring mutation in the ER from a tamoxifen-stimulated transplantable human breast tumor line. The mutation is at AA351 of LBD, where the aspartate is changed to tyrosine (Asp351Tyr). In this report, we compared and contrasted the pharmacology of raloxifene to block or induce E2-stimulated increase in TGF-alpha mRNA in stable transfectants of ER-negative human breast cancer cells with the cDNAs from wild-type, mutant-amino acid (AA) 400 ER and mutant-AA 351 ER. Our results show that the mutation at AA 351 that replaces aspartate by tyrosine specifically changes the pharmacology of raloxifene from an antiestrogen to an estrogen. By contrast, a mutation at AA 400 does not, and the antiestrogenic properties of raloxifene are retained. These data and the fact that the nitrogen in the side chain must specifically interact with aspartate 351 makes this the key to the antiestrogenic activity of raloxifene.  相似文献   

5.
6.
Doisynolic acids are non-steroidal estrogenic compounds originally obtained from alkali fusion of estrone and equilenin. Z-bisdehydrodoisynolic acids (Z-BDDA) exhibit a low binding affinity accompanied by a disproportionately high biologic activity. Two experiments were designed to investigate the chronic effects of (+)-, (-)- and (+/-)-Z-BDDA and (+)-17beta-estradiol (E2) in male and female rats. The (+)-, (-)- and (+/-)-forms Z-BDDA were prepared and injected, daily for four to six weeks into male and female rats and changes in body weight, food intake, metabolic parameters, and reproductive parameters were investigated. Results from both experiments demonstrate that in male and female rats, (+)- and (+/-)-Z-BDDA had similar estrogenic effects on reproductive organ weight. Surprisingly, (-)-Z-BDDA did not induce the increase in uterine weight observed with (+)- and (+/-)-Z-BDDA and E2, demonstrating selective estrogen receptor modulation (SERM). Beneficial metabolic effects, although compound- and gender-specific, included a significant weight repression, reduction in cholesterol, reduction in blood glucose, and positive alterations in body fat distribution. Future research defining the optimal dosages of (-)-Z-BDDA that will maximize beneficial effects and minimize undesirable effects on reproductive tissues will lead to more efficacious treatment options for endocrine-responsive conditions in males and females.  相似文献   

7.
Multiple health benefits have been postulated for the long-term use of hormone therapy in postmenopausal women, most notably for prevention of osteoporotic fractures and coronary heart disease, as well as several risks, including cancer of the breast and uterus and venous thromboembolism. Cardiovascular disease is the most common cause of death among postmenopausal women. If real, the reduction in risk of coronary heart disease by hormone use suggested by observational studies would likely outweigh the risks. The decision to initiate and maintain hormone therapy is complicated by uncertainties about estrogen's true benefits and risks. Raloxifene, a selective estrogen receptor modulator (SERM), appears to have many of the benefits of estrogen without the cancer risks. It is not known if SERMs can provide significant cardiovascular protection. This article reviews the relation of use of postmenopausal hormones and raloxifene to women's health and addresses the need for large randomized trials to quantify the effect of both postmenopausal estrogen and raloxifene on cardiovascular health.  相似文献   

8.
BACKGROUND: The beneficial effect of long-term hormone replacement therapy in terms of a decreased risk of cardiovascular disease is now generally accepted. Raloxifene, a selective estrogen receptor modulator, has demonstrated hypolipidemic properties while leaving the endometrium unstimulated. METHODS AND RESULTS: For our study of the effects of raloxifene on atherosclerosis, 75 rabbits were ovariectomized and treated with either raloxifene, 17beta-estradiol, or placebo; 25 rabbits were sham operated and treated with placebo. After 45 weeks, the raloxifene group had two thirds of the aortic atherosclerosis, as evaluated by the cholesterol content of the proximal inner part of the aorta, found in the placebo group (placebo, 577+/-55.1 nmol/mg protein; raloxifene, 397+/-53.6 nmol/mg protein; P<.05); the estrogen group had one third of the aortic atherosclerosis in the placebo group (estrogen, 177+/-32.1 nmol/mg protein; P<.001). The sham-operated group (473+/-59.6 nmol/mg protein) was not significantly different from placebo. These effects were only partly explained by the changes in serum lipids and lipoproteins, and treatment with both estrogen and raloxifene independently predicted the response in aorta cholesterol. Because plasma levels of total raloxifene were low relative to clinical values in postmenopausal women, dose-response data for raloxifene are required. CONCLUSIONS: Our findings indicate that raloxifene hydrochloride has a potentially important antiatherogenic effect, analogous to that observed with estrogen in this model.  相似文献   

9.
Previous studies have shown that the calcitonin gene-related peptide (CGRP) immunoreactivity in the central nervous system (CNS) of adult rats is sexually dimorphic and regulated by sex steroid. In the present study, we used immunocytochemistry to investigate the sex difference in CGRP-immunoreactive (IR) neurons in rat dorsal root ganglia (DRG). The numbers of CGRP-IR neurons at the cervical, lumbar and sacral levels in the female rats were significantly lower than those of the male rats. We also found that the number of CGRP-IR neurons at the lumbar level was increased in ovariectomized (OVX) rats, but was decreased in estradiol (E2)-treated rats (OVX+E2). A large number of estrogen receptor (ER)-IR neurons at the lumbar level were found in the female rats, and its number was greater than that in the male rats. We also investigated the change in the number of ER-IR neurons of OVX rats after estrogen treatment. The number of ER-IR neurons in the OVX+E2 rats was consistent with that of the intact female rats, but was significantly increased in the OVX rats. As shown by a double-labeling immunocytochemical method, over 80% of the CGRP-IR neurons at the lumbar level showed ER immunoreactivity in the female, OVX and OVX+E2 rats, compared to only about 46% in the male rats. These results indicate that there is a gender difference in CGRP expression in the rat DRG, and that this CGRP expression might be downregulated by estrogen (at least in part) through its receptor.  相似文献   

10.
Raloxifene has been shown to have estrogen agonist effects on bone and cholesterol metabolism while having estrogen antagonist effects on mammary gland and uterus. Reported here are the results of a study to determine whether raloxifene had the estrogen agonist effect of inhibiting coronary artery atherogenesis and to compare its effects with those of traditional conjugated equine estrogens (CEE) treatment. Ovariectomized (surgically postmenopausal) cynomolgus monkeys were fed a moderately atherogenic diet and treated with a placebo, raloxifene (1 mg/kg x day), raloxifene (5 mg/kg x day), or CEE (Premarin) at a dose that mimicked that of 0.625 mg/day in women. The effects of raloxifene on plasma lipid concentrations were generally comparable to those reported in postmenopausal women treated with raloxifene: reductions in low density lipoprotein cholesterol concentrations and no significant effects on high density lipoprotein cholesterol. We found no evidence that raloxifene had an estrogen agonist effect on coronary arteries. Treatment with CEE resulted in about a 70% reduction in coronary artery plaque size relative to that in the placebo group, whereas neither the low nor the high dose of raloxifene had an effect on coronary artery plaque size. The low dose raloxifene group had about 2 times more atherosclerosis and the high dose group had about 3 times more atherosclerosis than the CEE group.  相似文献   

11.
Studies were performed to determine if the nonsteroidal anti-inflammatory drug ibuprofen alters bone and mineral metabolism in female rats. In experiment 1, four groups of growing rats underwent either sham operation or ovariectomy (OVX). One week later, controlled-release pellets with ibuprofen or placebo were implanted subcutaneously at the back of the neck. Following 3 weeks of treatment, rats were sacrificed and blood and bone samples were removed for serum assays and histomorphometric analysis. Body growth rate and the static cortical bone measurements made at the tibial diaphysis did not change in response to OVX. OVX, however, did increase radial bone growth, lowered serum 17beta-estradiol, reduced uterine weight, and decreased the cancellous bone area of the tibial metaphysis in the rats. Ibuprofen did not alter serum 17beta-estradiol or uterine weight but reduced radial bone growth as well as cancellous bone area of the tibial metaphysis in both sham-operated and OVX animals. In experiments 2 and 3, we tested the influence of ibuprofen on the effects of the tissue-selective estrogen agonist tamoxifen and of exogenous 17beta-estradiol in the OVX rat. Ibuprofen completely blocked the effects of tamoxifen and partially blocked the effects of 17beta-estradiol to prevent cancellous osteopenia. In contrast, ibuprofen did not influence the effects of tamoxifen and 17beta-estradiol to reduce radial bone growth. Besides the skeletal effects, ibuprofen suppressed estrogen-induced uterine growth. Our data suggest that ibuprofen blocks selective estrogen receptor-mediated activities in the rat.  相似文献   

12.
We investigated the interaction of bisphenol A (BPA, an estrogenic environmental contaminant used in the manufacture of plastics) with the estrogen receptor alpha (ERalpha) transfected into the human HepG2 hepatoma cell line and expanded the study in vivo to examine the effect of BPA on the immature rat uterus. Bisphenol A was 26-fold less potent in activating ER-WT and was a partial agonist with the ERalpha compared to E2. The use of ERalpha mutants in which the AF1 or AF2 regions were inactivated has permitted the classification of ER ligands into mechanistically distinct groups. The pattern of activity of BPA with the ERalpha mutants differed from the activity observed with weak estrogens (estrone and estriol), partial ERalpha agonists (raloxifene or 4-OH-tamoxifen), or a pure antagonist (ICI 182, 780). Intact immature female Sprague-Dawley rats were exposed to BPA alone or with E2 for 3 days. Unlike E2, BPA had no effect on uterine weight; however, like E2, both peroxidase activity and PR levels were elevated, though not to the level induced by E2. Following simultaneous administration, BPA antagonized the E2 stimulatory effects on both peroxidase activity and PR levels but did not inhibit E2-induced increases of uterine weight. These results demonstrate that BPA is not merely a weak estrogen mimic but exhibits a distinct mechanism of action at the ERalpha.  相似文献   

13.
The estrogen receptor (ER) mixed agonists tamoxifen and raloxifene have been shown to protect against bone loss in ovariectomized rats. However, the mechanism by which these compounds manifest their activity in bone is unknown. We have used a series of in vitro screens to select for compounds that are mechanistically distinct from tamoxifen and raloxifene in an effort to define the properties of an ER modulator required for bone protection. Using this approach, we identified a novel high affinity ER antagonist, GW5638, which when assayed in vitro functions as an ER antagonist, inhibiting the agonist activity of estrogen, tamoxifen, and raloxifene and reversing the "inverse agonist" activity of the pure antiestrogen ICI182,780. Thus, GW5638 appears to function as an antagonist in these in vitro systems, although in a manner distinct from other known ER modulators. Predictably, therefore, GW5638 alone displays minimal uterotropic activity in ovariectomized rats, but will inhibit the agonist activity of estradiol in this environment. Unexpectedly, however, this compound functions as a full ER agonist in bone and the cardiovascular system. These data suggest that the mechanism by which ER operates in different cells is not identical, and that classical agonist activity is not required for the bone protective activity of ER modulators.  相似文献   

14.
For the first time, raloxifene or alendronate was administered to rats immediately after ovariectomy for 10 months and compared with estrogen to elucidate mechanisms behind the raloxifene effects observed in nonreproductive and reproductive tissues. Specifically, 75-day-old rats were randomly selected as sham controls (Sham), ovariectomized controls (Ovx) or ovariectomized rats treated with fully efficacious doses of raloxifene (RA), 17 alpha-ethynyl estradiol (EE2) or alendronate (ABP). Lumbar vertebrae and proximal tibiae were examined by computed tomography (QCT) and by histomorphometry. Histomorphometry showed differences in bone architecture between groups when QCT densities were similar, but tibial trabecular bone analysis by QCT correlated with histomorphometry with r = .86 to .93, depending on the parameter. Both techniques confirmed that Ovx had substantially less bone than Sham, with greater loss of trabecular bone in the proximal tibia than vertebrae. Both techniques showed that RA had effects similar to but not identical with EE2 in preventing bone loss in vertebrae and tibiae. ABP partially prevented loss of bone in L-5, but was not significantly different from Ovx in the proximal tibia. This may be caused by ABP suppression of bone apposition, beyond effects observed for EE2 or RA. RA appeared to be more similar to EE2 because ABP significantly depressed bone formation (bone formation rate, mineral apposition rate) to below RA or EE2 levels, especially in L-5. Mechanical loading to failure of L-6 vertebrae showed a rank order of vertebral strength of Sham > RA > EE2 > Ovx > ABP, although significant differences were not observed between treatment groups. These data show that ABP suppression of bone formation can affect bone quality with long-term treatment. In other tissues, RA had minimal uterine effects, while significantly lowering serum cholesterol to below EE2-treated levels. Both EE2 and RA rats had significantly lower body weights than the other groups. ABP had no effect on serum lipids, uterine weight or body weight. Therefore, RA appears to have a broader range of desirable effects on bone, body weight, uteri and cholesterol than ABP or EE2 in ovariectomized rats.  相似文献   

15.
The ovariectomized (OVX), lactating rat model has been used to investigate the skeletal effects of the plant estrogen, genistein, over a 14-day period. The OVX, lactating rat on a low-calcium diet loses slightly more than 50% of its bone mineral mass during the first 2 weeks of lactation, and we have demonstrated that estrogen treatment can significantly reduce the loss of femoral mass (ash weight). Following OVX, the rats were assigned to treatment or control groups (both placebo and positive control with estrogen replacement). The treatment groups received one of three doses of a genistein-rich preparation each day via the feed for 2 weeks, after which time the pups began to have an interest in solid feed. A positive control group received conjugated estrogen in the feed. The genistein doses were: low (0.5 mg/d); intermediate (1.6 mg/d); and high (5.0 mg/d). Measurements included ash weights of the femur, scanning electron microscopy (SEM) of the proximal tibia, and uterine weights. SEM results were as follows: (1) at the low dose genistein was approximately equally effective to estrogen in the retention of cancellous bone tissue, as reflected in the number and density of trabeculae in hemisections of the tibial subepiphyseal region, but at high doses genistein was less effective; and (2) rats treated with low-dose genistein, like estradiol, had rougher endosteal surfaces and smaller pores on these surfaces than untreated control rats. Mean ash weights of the entire femur were highest in the rats treated with the low dose compared to control rats (P < 0.05), and they were higher than ash weights of rats administered the intermediate or high doses of genistein. The mean ash weights of the femurs were consistent with the genistein effects on the tibias observed by SEM. In summary, a biphasic response to the genistein preparation was found in this OVX rat model. Interpretation of the results suggests that, at the low dose, genistein appears to be an agonist at the estrogen receptor locus, whereas at higher doses the genistein is less effective and may even have adverse effects on bone cells. These findings of a biphasic effect of genistein (i.e., an inverted U effect) are consistent with those of other recent reports in the literature on isolated bone cells and on reproductive tissues. In summary, lower doses of genistein from soy foods would be expected to act similarly to estrogens with a beneficial effect on bone tissue, but at high doses that are unlikely to be consumed in human diets, this soy derivative may have potentially adverse effects on bone cell functions and thereby on bone tissue.  相似文献   

16.
Effects of age and ovariectomy (OVX) at birth on uterine growth, endometrial development, and estrogen receptor (ER) expression were determined for intact and OVX gilts (n = 5 per day) hysterectomized on postnatal days (PND) 0, 15, 30, 60, 90, or 120. Uteri were evaluated histologically, and ER protein and mRNA expression were characterized immunohistochemically and by in situ hybridization. OVX did not affect uterine weight or endometrial thickness until after PND 60, when both increased more rapidly in intact gilts. Neither did it affect genesis of uterine glands, which were present and which proliferated after PND 0, or endometrial ER expression patterns in glandular epithelium (GE), luminal epithelium (LE), or stroma (S) between PND 0 and 120. Endometrium was ER negative at birth. On PND 15, the ER signal was strong in GE, weak in S, and effectively absent in LE. Thereafter, although the ER signal remained strong in GE and increased through PND 60 in S, it was not evident consistently until after PND 30 in LE. The data indicate that 1) porcine uterine growth and endometrial morphogenesis are ovary-independent processes before PND 60; 2) uterine gland genesis is associated temporally with development of ER-positive endometrial GE and S; and 3) regulation of endometrial ER expression is ovary independent between PND 0 and 120. The results establish the ER as a marker of GE differentiation and implicate this receptor in mechanisms regulating endometrial morphogenesis in the neonatal pig.  相似文献   

17.
Study was carried out an Wistar female rats to evaluate the consequences of ovariectomy and 17 beta-estradiol substitutive treatment during aging on bone. Ca metabolism and calciotropic hormones. Three groups of fifteen rats, mature, old and senescent (4-, 10-, and 28 month-old) female were fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi, Within each group, 10 rats were surgically ovariectomized (OVX). From day 1 until day 60 after OVX, they were subcutaneously injected with either 17 beta-estradiol (E: 10 micrograms/kg BW/48 h; n = 5) or with solvent alone (OVX; n = 5). Five other rats were sham operated (SH) and received solvent alone. Animals were put in balance 1 day per week to determine Ca and Pi intestinal apparent absorption and urinary pyridinium cross-links excretion was measured by HPLC. All rats were killed by exsanguination 60 days after OVX. Plasma was collected for measurement of intact parathyroid hormone (PTH), calcitonin (CT), insulin-like growth factor-1 (IGF-1), Ca and Pi. The success of OVX was confirmed at necropsy by observation of marked atrophy of the uterine horns. The right femur was collected, cleaned from adjacent tissue and used for mineral analysis. Despite correct matching for feeding, BW was significantly larger in 6 and 12 month-old OVX rats. OVX and 17 beta-estradiol had no significant effect upon plasma Ca, Pi and CT concentrations. Aging is associated with increased circulating PTH levels (pg/ml) (SH-6 months: 50.8 +/- 12.6; 12 months: 219.1 +/- 34.9; 30 months: 158.7 +/- 23.5; P < 0.05). Urinary and fecal Ca and Pi excretion in senescent animals were higher than in adult or old rats, thus resulting in a drastic fall in both intestinal apparent absorption and retention of Ca and Pi in 30 month-old animals. In each group, urinary pyridinium cross-links excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. In the same way, OVX increased and estrogen decreased the plasma IGF-1 levels. We conclude that 17 beta-estradiol prevents high turnover-induced osteopenia even in 30 month-old rats.  相似文献   

18.
The interaction of estrogen and androgen was studied at the estrogen receptor level of adult rat uterus by the in vivo experiment. Both the free and total estrogen receptor in the cytosol and nucleus were assayed by the controlled pore glass beads method [2]. Testosterone was given by daily injection for 5 days to the rats treated with estradiol dipropionate (long-acting estradiol) 3 or 5 days before. In the estradiol dipropionate-treated rats the plasma estradiol concentration remained at an extremely high level for 7 days and then decreased to 5-fold of that of proestrus control by the 14th day. There was no significant change in the uterine estrogen receptor of the adult rat with a high estradiol concentration induced by testosterone.  相似文献   

19.
Treatment with pharmacological doses of estrogen is the most potent way to stimulate hepatic LDL receptor expression in vivo. The mechanism for this effect is unclear, in part because of difficulties in inducing this stimulation in vitro. A fundamental question, whether estrogen receptors (ERs) mediate this stimulation, has not been addressed. The aim of the current study was to determine the involvement of ERs in the estrogen-induced stimulation of LDL receptors. Treatment of rats with high doses of ethynylestradiol for 7 days increased the hepatic LDL receptor protein and mRNA levels four- and threefold, respectively. LDL receptor stimulation in estrogen-treated rats was not due to their reduced food intake because hepatic LDL receptor expression did not increase in rats fasted for 72 hours. Treatment with antiestrogen (tamoxifen or clomiphene) abolished the LDL receptor stimulatory effect of ethynylestradiol at both the protein and mRNA levels. Antiestrogen alone had no effect on hepatic LDL receptor expression and did not influence the strong resistance to dietary cholesterol normally present in rats. It is concluded that ERs are critically involved in the induction of hepatic LDL receptor expression by ethynylestradiol. The known role of growth hormone for the expression of hepatic ERs may therefore play a role in the modulation of the effects of estrogen on cholesterol metabolism and hepatic LDL receptors in the rat.  相似文献   

20.
For the first time testosterone is shown to be an important regulator of the insulin-like growth factor-I (IGF-I) in the rat uterus under in vivo conditions. In this study the regulation of IGF-I and the estrogen receptor (ER) by gonadal steroids in the uterus and liver of female rats was monitored. The ER level was assayed by hormone binding after treatment with testosterone, 5 alpha-dihydrotestosterone or estradiol and specific mRNA species were analyzed by a solution hybridization/RNase protection assay using 35S-labeled RNA probes. Ovariectomized rats restored uterine weight after treatment with testosterone. Uterine IGF-I mRNA was more than 20-fold higher in testosterone treated rats compared to untreated ovariectomized controls after 48 h treatment. The effects of testosterone on ovariectomized animals was followed in a timecourse study. Testosterone administration increased uterine IGF-I mRNA expression during the first 48 h and the maximally induced level was maintained throughout the duration of the experiment (168 h). Since induction of IGF-I mRNA by estrogen is transient, these data indicate that androgen and estrogen increase IGF-I mRNA by different mechanisms. Regulation of IGF-I mRNA by gonadal steroids was also studied in hypophysectomized animals. The rats were given either testosterone, 5 alpha-dihydrotestosterone or estradiol, and uterine IGF-I mRNA was measured after 1 week of treatment. At this timepoint estrogen treated rats showed levels of IGF-I mRNA not significantly different from those of hypophysectomized controls. In contrast testosterone and 5 alpha-dihydrotestosterone increased the IGF-I mRNA level 30 and 40 times, respectively, relative to hypophysectomized control animals. Since 5 alpha-dihydrotestosterone is not convertable to estrogen, the induction by testosterone was considered to be a true androgenic phenomenon.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号