Assessment of non-target toxicity effects of synthetic estradiol, quinestrol, in chickens.

Fertility control agents for the management of rodent populations are developing and maturing. Investigating the impacts on non-target species of consumption of these agents is essential. The present study assessed the non-target toxicity effects of quinestrol, a synthetic estrogen-based antifertility agent for managing rodent populations. Various quinestrol doses administered to male and female (n = 60 each) chickens through single oral gavage were 0 (A), 10 (B), 50 (C), and 150 (D) mg/kg body weight. Chickens were assessed for effect on body weight, weight of vital and reproductive organs, reproductive hormones, histology of reproductive organs and egg laying rates after 15, 30, and 135 days of treatment. Quinestrol did not induce mortality in chickens and its effects were time and dose dependent. The 90% egg-laying rates were delayed by 30, 60 for groups B and C compared with the control group, and group D did not reach the 90% egg-laying rate by 135 days. Reproductive organs in males and females returned to normal levels within 30 and 135 days, respectively. With the exception of the FSH concentration in group D, reproductive hormones of both sexes were similar to controls by 30 days. No other significant effects were found. The present research demonstrated the safety of quinestrol on non-target species and facilitates recommendations for the general administration of quinestrol for rodent pest management.

Reproductive responses of rice field rats (Rattus argentiventer) following treatment with the contraceptive hormones, quinestrol and levonorgestrol.

The rice field rat, Rattus argentiventer, is a significant pest of rice in Southeast Asia. Fertility control methods have the potential to provide safe and effective alternatives to control methods that often include indiscriminate use of rodenticides or electric barriers. The aim of this laboratory study was to assess uptake of bait coated with different concentrations of the contraceptive hormones, quinestrol (E) and levonorgestrel (P), delivered alone and in combination (i.e. EP-1) and determine the short-term effects on reproductive parameters of adult male and female R. argentiventer. In Experiment 1, 2 concentrations of E, P, and EP-1 (10, 20 ppm) were fed to groups of wild-caught rats for 7 days. In females, both E and EP-1 induced uterine edema. In males, EP-1 reduced epididymis and seminal vesicle weights and lowered sperm motility. However, these responses were inconsistent due to low bait acceptance, especially with increasing concentrations. In Experiment 2, EP-1 (0, 20, 50, 100 ppm) was administered by oral gavage daily for 7 days to male R. argentiventer. There were significant reductions in epididymal and seminal vesicle weights for all oral doses of EP-1, in sperm counts for the 50 ppm dose, and in sperm motility for the 20 and 50 ppm doses compared to the control group. To select the optimum dose of EP-1, we must address the poor acceptance of contraceptive-coated baits by rice field rats. Further research is required to improve the palatability of EP-1 and to test its uptake under field conditions.

Ratio-dependent effects of quinestrol and levonorgestrel compounds (EP-1) on reproductive parameters of adult male Swiss mice.

Fertility control is considered as the second-generation pest rodent management strategy. Most previous studies have focused on the dosage-dependent effects of quinestrol and levonorgestrel compounds (EP-1) at a ratio of 1:2, but the ratio-dependent effects of EP-1 have not been fully investigated, especially in male rodents. To test the ratio-dependent antifertility effects of EP-1 with different ratios (1:2, 1:1, and 2:1) on male Swiss outbred strain of laboratory mice, forty male mice were randomly assigned into four groups (n = 10). Mice in the three treatment groups were provided one of the three EP-1 mixture compounds for 3 successive days via gavage at a dosage of 50 mg/kg(body weight), and then all mice were sacrificed 15 days after the gavage treatment. Reproductive organ weights, sperm density and motility, levels of testosterone (T), estradiol (E2), luteinizing hormone (LH), and follicle stimulating hormone (FSH) in serum and/or testis, and androgen receptor (AR), estrogen receptor α (ERα), estrogen receptor ß (ERß), luteinizing hormone receptor (LHR), and aromatase in testis were determined. Each of the ratios of quinestrol and levonorgestrel significantly decreased the density and motility of sperm and induced atrophy of the epididymis and seminal vesicle. The combination of compounds also significantly reduced serum T and LH levels, increased testicular T levels and decreased testicular estradiol ERß and aromatase levels. EP-1 delivered at a ratio of 1:1 induced the most significant effects on the reproductive parameters assessed and shows the potential for use in fertility control of male rodents.

Responses in reproductive organs, steroid hormones and CYP450 enzymes in female Mongolian gerbil (Meriones unguiculatus) over time after quinestrol treatment.

The aim of this study was to assess the effects and reversibility of the synthetic estrogen compound, quinestrol, on the reproductive organs, steroid hormones, and drug-metabolizing enzymes CYP3A4 and CYP1A2 in liver and kidney over time after two quinestrol treatments in female Mongolian gerbils (Meriones unguiculatus). Female gerbils were treated with 4mg/kg quinestrol (9 gerbils/group, 3 treated group) (1 control group, 0mg/kg) for 3days and treated again after 25days. Animals were killed for collection of samples at 5, 10 and 15days after the second treatment ending. Two interval quinestrol treatments significantly increased uterine weight, with trend of increase over time, but no change could be detected in ovarian weights. Quinestrol treatment increased progesterone and estradiol levels, both with trend of decline over time. Quinestrol increased liver and kidney weights and total enzyme content of CYP3A4 and CYP1A2, with trend of decline over time. On the basis of reversible changes of detoxification enzymes or organs, interval quinestrol treatment effectively and reversibly influenced the reproductive hormone and organ to some extent.

Effects of quinestrol on the vocal behavior of mice during courtship interactions.

Vocalizations are a crucial part of courtship and mating in a wide variety of species. Mating behavior, including courtship calls, is modulated by sex steroid hormones. Male mice produce courtship ultrasonic vocalizations to attract females during heterosexual encounters. However, rare is the knowledge on whether vocal behavior of mice changes under sterilant treatment which will affect gonadal hormone levels. In the present study, we treat male mice with quinestrol, which interferes with the release of the gonadotropin-releasing hormone (GnRH) and has a significant anti-fertility effect in rodents. We compared the differences in the syllable structures (including peak intensity, peak frequency, duration, and bandwidth), total number of calls, and harmonic syllable proportions between quinestrol treated and control male mice. Male mice treated with quinestrol produced more courtship calls and more harmonic syllables than control mice, whereas the parameters of call syllables showed no significant change between the two groups. The results indicate that normal male vocal behavior during sexual interactions could be retained or even reinforced after quinestrol treatment. In addition, female mice approached male mice treated with quinestrol more than control mice, suggesting that the treated male mice were more attractive to the female mice than the controls. Thus, competitive reproductive interference is enhanced. Further, findings provided behavior mechanism in vocal context of the fertility control in mice.

Recovery of fertility in quinestrol-treated or diethylstilbestrol-treated mice: Implications for rodent management.

Fertility control is an alternative strategy to traditional culling for the management of rodent pests. Previous studies have demonstrated that quinestrol is a potential contraceptive for male rodents, but the recovery of fertility in quinestrol-treated rodents has not been evaluated. This study used C57BL/6J mice to evaluate the recovery rate of male fertility after the administration of quinestrol. Diethylstilbestrol (DES), a non-steroid estrogenic compound, was used for comparison. Different groups of mice were treated with 1 mg/kg quinestrol, 1 mg/kg DES, or castor oil separately for 7 days. These mice were then killed on days 8, 22 and 50 respectively. Our results indicated that the weight of epididymides and seminal vesicles decreased significantly on days 8 and 22 in quinestrol/DES-treated mice, with extensive histological changes in the seminiferous tubules. Sperm concentrations in the cauda epididymal fluid were significantly reduced on days 8 and 22 in both quinestrol and DES treatment groups and on day 50 for the DES, but not the quinestrol group. Further analysis revealed that DES-treated mice exhibited a higher proportion of abnormal sperm accumulation in the epididymis, indicating that the normal sperm transportation to the cauda epididymis was blocked. Our results indicate that the anti-fertility effects on male mice given quinestrol were of shorter duration than for those receiving DES at the dose of 1 mg/kg body weight.

Mitochondrial- and Fas-L-mediated pathways involved in quinestrol induced spermatogenic apoptosis in adult rat testes.

The pathways involved in quinestrol-induced spermatogenic apoptosis were studied in adult male rat by using daily intragastric administration of 0.01 mg/kg, 0.1 mg/kg and 1 mg/kg body weight quinestrol for two consecutive weeks. The immunohistochemistry staining was performed to measure the expression of proliferating cell nuclear antigen (PCNA), caspase-3, Bax, Bcl-2, Fas and FasL. The results showed that testes weights and the size of seminiferous tubule (ST) decreased as well as the organization of the ST changed significantly after treatment with 1 mg/kg quinestrol. The number of germ cells expressing caspase-3, Bax, Fas and FasL markedly increased whereas the numbers of cells expressing Bcl-2 and PCNA significantly decreased in the group treated with quinestrol at 1 mg/kg compared with the control. The results suggest that quinestrol induced abnormal spermatogenesis through the mitochondrial- and Fas-L-mediated pathways after quinestrol exposure in male rat.

Quinestrol induces spermatogenic apoptosis in vivo via increasing pro-apoptotic proteins in adult male mice.

The effects of quinestrol on spermatogenesis were investigated in adult male mice by daily intragastric administration of quinestrol with various doses of 5, 10, 50 and 100mg/kg body weight for 10 days. The sperm counts declined while the number of abnormal spermatozoa went up in mice treated with quinestrol. The testicular weight and seminiferous tubular area gradually declined with increasing dosages of quinestrol to 50 and 100mg/kg. Rarefied germ cells showed irregular distributions in the seminiferous tubules of mice treated with 50 and 100mg/kg quinestrol. Apoptosis was highly pronounced in spermatogonia, spermatocytes, spermatids and Leydig cells. Antioxidant enzyme activities - superoxide dismutase and glutathione peroxidase - as well as total antioxidant capacity significantly reduced, while malondialdehyde contents increased. The number of germ cells expressing caspase-3, p53, Bax and FasL significantly increased whereas cells expressing Bcl-2 significantly decreased in groups treated with 50 and 100mg/kg quinestrol compared with the control. The concentration of nitrogen monoxidum also increased significantly under these dosages. The results suggest that quinestrol stimulates oxidative stress to induce apoptosis in spermatogenic cells through the mitochondrial and death receptor pathways in adult male mice.

Effects of quinestrol and levonorgestrel on prolactin serum concentration in lactating Mongolian gerbils (Meriones unguiculatus) and reproductive parameters of their offspring.

The effects of the two sterilants, quinestrol (QE) and levonorgestrel (LNG) on serum prolactin (PRL) level in lactating Mongolian gerbils and reproductive parameters of their offspring were examined in the study. Both sterilants increased the serum PRL level in lactating gerbils. The body weight as well as weights of the ovary, testis, epididymides, and seminal vesicles were lower, whereas that of the uterus was higher in the pups originating from QE-treated mothers in comparison to controls. Histological ovarian sections of the offspring from QE-treated mothers contained only growing follicles, whereas their uterine sections showed a thinner endometrium, thicker myometrium, and greater epithelial-cell height than in controls. The histometrical testis characteristics as well as sperm concentration and motility of male pups from QE-treated mothers were lower compared to those of the control group. The serum gonadotropin levels of female pups from mothers treated with QE were lower, whereas the serum estradiol (E(2)) and progesterone (P(4)) levels were higher than in control gerbils. In contrast, serum gonadotropin and testosterone (T) levels of male pups from QE-treated mothers were lower compared to controls. LNG did not affect the examined parameters of the offspring. The offspring from QE-treated mothers was infertile, whereas the offspring from LNG-treated mothers was fertile. In summary, QE and LNG have a stimulatory effect on PRL level in lactating gerbils. It also appears that QE administered via milk to mothers affects reproductive processes of their offspring.

Combined effects of levonorgestrel and quinestrol on reproductive hormone levels and receptor expression in females of the Mongolian gerbil (Meriones unguiculatus).

The effects of treatment with a combination of levonorgestrel and quinestrol (EP-1; ratio of 2:1) on reproductive hormone levels and the expression of their receptors in female Mongolian gerbils were examined. We show that serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) decreased, whereas serum estradiol (E2) and progesterone (P4) increased after EP-1 treatment. EP1 down-regulated mRNA expression of the follicle-stimulating hormone receptor (FSHR) and the estrogen receptor (ER) ßin the ovary. EP-1 up-regulated the mRNA expression of the luteinizing hormone receptor (LHR) and the progesterone receptor (PR) in the ovary as well as ERα and PR in the uterus of Mongolian gerbils. The effects were time-dependent and dose-dependent. EP-1 had no obvious effects on ERα mRNA expression in the ovary. The current study demonstrates that the effect of EP-1 on the expression of ER subtypes is tissue-specific in Mongolian gerbils. EP-1 disrupted the reproductive endocrinology of the Mongolian gerbil. These findings suggest that the effects of EP-1 on reproductive hormone levels and their receptor expression in Mongolian gerbils may be the result of synergistic actions of levonorgestrel and quinestrol, with quinestrol playing the major role.

Subfertile effects of quinestrol and levonorgestrel in male rats.

The contraceptive regimen consisting of levonorgestrel and quinestrol (EP-1) has been shown to be effective in several types of wild rodents. In the present study, we investigated the effect of EP-1 and its two components on fertility and spermatogenesis to elucidate the mechanisms underlying its contraceptive effect. Sprague-Dawley rats were treated with 0.33 mgkg(-1) quinestrol (E group), 0.67 mgkg(-1) levonorgestrel (P group) or their combination (EP group) for 7 days and then killed on Days 21 or 42 after treatment for tissue analysis. On Day 21, the weight of the cauda epididymis decreased significantly, while the weight of the adrenal gland increased significantly in the E and EP groups compared with the weights in the control group. In addition, there was a significant decrease in sperm number in the E and EP groups compared with the control group and there was less staining for the androgen receptor and Wilms' tumour nuclear protein 1 in the E and EP groups. The primary defects in E- or EP-treated rats were abnormal spermiogenesis, lack of elongating spermatids, and pachytene spermatocyte arrest. Analysis of MutL homologue 1 revealed that EP treatment inhibited chromosome recombination during meiosis, but did not cause obvious genetic abnormalities. These data demonstrate that quinestrol, alone or in combination with levonorgestrel, induces subfertility in male rats mainly by interfering with germ cell differentiation. Thus, EP-1 or E alone may be effective contraceptive regimens for fertility control in rodents.

Effects of quinestrol on reproductive hormone expression, secretion, and receptor levels in female Mongolian gerbils (Meriones unguiculatus).

Quinestrol, a synthetic estrogen with marked estrogenic effects and prolonged activity, has potential as a contraceptive for Mongolian gerbils. The objective of this study was to describe the effects of quinestrol on reproductive hormone expression, secretion, and receptor levels in female Mongolian gerbils. Serum and pituitary concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were decreased, whereas serum concentrations of estradiol (E2) and progesterone (P4) were increased after quinestrol treatment; the effects were both time- and dose-dependent. Furthermore, quinestrol downregulated expression of FSHß and LHß mRNA in the pituitary gland, as well as FSH receptor (FSHR) and estrogen receptor (ER) ß in the ovary. However, it up-regulated mRNA expression levels of ERα and progesterone receptor (PR) in the pituitary gland and uterus, as well as mRNA for LH receptor (LHR) and PR in the ovary (these effects were time- and dose-dependent). In contrast, quinestrol had no significant effects on the mRNA expression levels of ERα in the ovary, or the gonadotropin α (GtHα) subunit in the pituitary gland. We inferred that quinestrol impaired synthesis and secretion of FSH and LH and that the predominant ER subtype in the pituitary gland of Mongolian gerbils may be ERα. Overall, quinestrol disrupted reproductive hormone receptor expression at the mRNA level in the pituitary-gonadal axis of the Mongolian gerbil.

Inhibitive effects of quinestrol on male testes in Mongolian gerbils (Meriones unguiculatus).

The current study evaluated effects of quinestrol on oxidative stress and abnormal spermatogenesis for male Mongolian gerbils. Gerbils were randomly divided into multi-dose treated, single-dose treated, control groups. At 15 days after treatment antioxidant enzymes (SOD, GSH-Px) activities and T-AOC were decreased whereas the MDA concentration was significantly increased, testicular weight and seminiferous tubular areas decreased, germ cells were rarefied and showed irregular distribution in seminiferous tubules, apoptosis was pronounced among spermatocytes and spermatids, the number of dead and abnormal acrosomes of spermatozoa increased significantly in quinestrol treated groups. At 30 days following treatment the testicular histopathological changes were more severe, sperm quality and antioxidant capacity continued to decline, and multi-dose treatment produced more damage to gerbils testes compared with single-dose treatment. The physiological indicators were recovered by 60 days of treatment withdrawal. The results showed oxidative stress induced by quinestrol in relation to abnormal spermatogenesis.

Effects of quinestrol as a contraceptive in mongolian gerbils (Meriones unguiculatus).

The contraceptive effects of quinestrol in Mongolian gerbils were examined. The results showed that body weight significantly increased after quinestrol treatment, except in the group that received the highest dose. The gonadosomatic index of ovaries decreased, whereas that of uteri increased, and uterine edema appeared after quinestrol treatment. Histological examination revealed that the ovaries had a lack of mature follicles and corpora lutea and that the myometrium and endometrium of the uteri became thin after quinestrol treatment. Persistent estrous appeared after quinestrol treatment, and time to persistent estrous shortened with increasing doses of quinestrol. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels decreased, whereas estradiol (E2) and progesterone (P4) levels increased after quinestrol treatment, and the effects were dose-dependent. During gestation, the serum E2 levels in the different treatment groups were not significantly different. During gestation in the control groups, the serum P4 levels from days 0 to 15 were higher than in the quinestrol-treated groups; however, they did not show significant differences from days 18 to 24. Doses of 0.1 to 2.7 µg/g quinestrol over 6 days completely inhibited fertility. Birth time was prolonged with increasing doses of quinestrol. The findings suggest that quinestrol has marked estrogenic effects in Mongolian gerbils and may inhibit follicle maturation and ovulation through lowered gonadotropin levels. Uterine edema and abnormal E2 and P4 levels during gestation are important causes of pregnancy failure in quinestrol-treated Mongolian gerbils. Quinestrol causes prolonged inhibition of fertility in Mongolian gerbils.

Behavioral evaluation of quinestrol as a sterilant in male Brandt's voles.

The theoretical, ecological, physiological, and mathematical aspects of fertility control in mammals have already been well studied, but little attention has been given to the behavioral effects, especially in rodents. We investigated the effects of quinestrol, a synthetic estradiol analog, on social behavior and reproductive physiology in male Brandt's voles (Lasiopodomys brandtii). Over seven successive days, four concentration gradients of quinestrol (none, 0.001%, 0.003%, and 0.006%) were separately mixed into feed and provided to male Brandt's voles. Reproductive parameters, including the reproductive organ indexes, testosterone level and reproductive ability, were observed and collected 2 weeks after finished feeding treatment and again after 4 weeks. Dyadic social encounters and female preferences were then recorded for the control males (no quinestrol) and the highest concentration group (0.006%). Results showed that quinestrol reduced the consumption of feed. Physiological data revealed that quinestrol had also effectively reduced the reproductive organs indexes, testosterone levels, female pregnancy rates and litter size. This phenomenon was especially evident in the highest concentration group only after 2 weeks of feeding. Behavioral results showed that both frequency and duration of female preference were unbiased between control and treated males. In social conflict tests, control pairs (CC) had lower latency toward initial attack than treated pairs (TT) and pairs of one control and one treated male (CT). Among the three pairs, there was no evident difference in patterns of mutual attack and agonistic behavior. In CT pairs, sterile males have the same winning rate and agonistic behavior as control males. Our data revealed that quinestrol has anti-fertility capabilities with little behavioral side effects on Brandt's voles, which suggested quinestrol's potential as a sterilant for Brandt's voles. The palatability, however, should be improved before field practice.

[Effect of nylestriol and levonorgestrel on the expression of estrogen receptor subtypes in human osteosarcoma MG-63 cell lines].

OBJECTIVE: To observe the effect of different concentrations of nylestriol (NYL) and levonorgestrel (LNG) on the expression of ERα and ERß in human osteoscarcoma MG-63 cell lines, and to explore the impact of paracrine effect on the gene expression. METHODS: MG-63 cells were treated with 3 concentrations (10(-10),10(-8), and 10(-6) mol/L) of NYL or LNG. The untreated control group and the positive control group were also established. The 2 groups treated with NYL (10(-10) mol/L) or LNG (10(-8) mol/L) were designed to renew the medium every 12 h. Semi-quantitative RT-PCR was conducted to detect the mRNA expression of ERα and ERß on the MG-63 cells treated with different concentrations of the 2 drugs, respectively. RESULTS: Both drugs up-regulated ERα and ERß mRNA expression. The best concentration for both NYL and LNG was 10(-6) mol/L for ERα expression. As for ERß, the best concentration of NYL and LNG was 10(-10) mol/L and 10(-8) mol/L. The role of medium replacement on the expression of ERα was not observed, but medium replacement inhibited ERß expression. CONCLUSION: Both NYL and LNG can up-regulate the mRNA expression of ER subtypes in MG-63 cells, with mutual restriction between the 2 subtypes. The paracrine effect on MG-63 cell lines may be involved in the regulation process of mRNA expression of ERß.

Antiosteoporotic activity of icariin in ovariectomized rats.

Icariin was evaluated for its antiosteoporotic activity in an ovariectomized rat model of osteoporosis. The rats were divided into sham and OVX groups. The OVX rats were then subdivided into five groups treated with water, nylestriol (1 mg/kg body weight, weekly, orally) or icariin (ICA) (5, 25, and 125 mg/kg body weight, daily, orally) for 12 weeks. In OVX rats, the increases of body weight, serum BGP and ALP were significantly decreased by ICA treatment. In OVX rats, atrophy of uterus and descent of BMD were suppressed by treatment with ICA. In addition, ICA (125 mg/kg body weight) completely corrected the decreased serum concentration of Calcium, Phosphorus, and E(2) observed in OVX rats. ICA (125 mg/kg body weight) increased biomechanical strength significantly in comparison to the sham group. Histological results also showed its protective action through promotion of bone formation. The findings, assessed on the basis of biochemical, bone mineral density, biomechanical, and histopathological parameters, showed that ICA has a definite antiosteoporotic effect, similar to estrogen, especially effective for prevention bone fracture induced by estrogen deficiency.

[Protective effect of purariae isoflavone on apoptosis cells of nasal mocosas in ovariectomized rats].

OBJECTIVE: To study the protective effect of purariae isoflavone on apoptosis cells of atrophic nasal mucosas in ovariectomized rats. METHOD: 60 rats were divided into four groups as control, ovariectomized, ovariectomized + nylestriol (O + N) and ovariectomized + purariae isoflavone (O + P), each with 15 rats. Earlier apotosis cells of mucosas taken from nasal septum were measured with flow cytometry. RESULT: Compared with control group, and the number of apoptosis cells of mucosas increased after being ovariectomized,and the number of apoptosis cells of mucosas in O + N and O + D group didn't change. CONCLUSION: Nylestriol and purariae isoflavone might have effects on protecting cells of mucosas from lacking of estrogen by decreasing apoptosis cells in ovariectomized rats.

[Protective effect of estrogens replacement on apoptosis cells of nasal mocosas in ovariectomized rats].

OBJECTIVE: To study the protective effect of nylestriol on apoptosis cells of atrophic nasal mucosas in ovariectomized rats and the difference between nasal drip and gastrogavage. METHOD: Sixty rats with atrophic rhinitis were divided into four groups at random (each with 15 rats): contrary group (Cg), ovariectomized group (Og), ovariectomized + nylestriol nasal drip group (ONNDg), and ovariectomized + nylestriol by gastrogavage (ONGg). Earlier apoptosis cells of nasal mucosas taken from nasal septum were measured with flow cytometry. RESULT: After being ovariectomized, the number of apoptosis cells of mucosas increased. In ONGg, the number of apoptosis cells of mucosas increased at 15 d after operation (P < 0.05), but it recovered at 30 d and 60 d after operation. In ONGg, the number of apoptosis cells of mucosas increased at 15 d and 30 d after operation (P < 0.05), but it recovered at 60 d after operation. CONCLUSION: Estrogen replacement by gastrogavage and via nasal drip have effects on protecting cells of mucosas from lacking of estrogen by decreasing apoptosis cells in ovariectomized rats. It might cost more time to get therapeutic effectiveness via nasal drip than by gastrogavage.

[Effect of nylestriol on bone remodeling in ovariectomized rats].

OBJECTIVE: To clarify the effects of nylestriol on microarchitecture and interleukin-6 (IL-6) mRNA expression in tibial bone in ovariectomized rats. METHODS: 30 female rats were randomly allocated into 3 groups: sham, OVX and nylestriol-treated group. Nylestriol-treated group were ovariectomized, then fed with nylestriol for 3 months and the bone mineral density (BMD) was measured in lumbar vertebra by dual energy x-ray absorptiometry. After sacrifice of the animal, bone histomorphometric parameters were measured to study the changes in bone microarchitecture, and RT-PCR was performed to detect the expression of IL-6 mRNA in bone tissue. RESULTS: BMD was significantly reduced, while IL-6 mRNA level elevated in the OVX group compared with the sham group. Static histomorphometric data showed that the trabecular bone volume, mean trabecular plate thickness and density were reduced while the mean trabecular plate space elevated remarkably in the OVX group in comparison with that in the sham group. As for dynamic parameters, trabecular osteoid surface, tetracyclin labeled surface and bone turnover rate were increased while osteoid maturation rate decreased significantly in the OVX group compared with the sham group. BMD, IL-6 mRNA expression and bone histomorphometric parameters were improved in nylestriol-treated rats. CONCLUSION: Nylestriol plays an important role in maintaining bone volume and improving bone microarchitecture by markedly inhibiting bone turnover and bone resorption, which might be to some degree attributed to reduced IL-6 expression.