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OVX Rats (ovx + rat)
Selected AbstractsRANKL Inhibition with Osteoprotegerin Increases Bone Strength by Improving Cortical and Trabecular bone Architecture in Ovariectomized Rats,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008Michael S Ominsky Abstract Introduction: Ovariectomy (OVX) results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. We examined whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in OVX rats. Materials and Methods: Rats were OVX or sham-operated at 3 mo of age. Sham controls were treated for 6 wk with vehicle (Veh, PBS). OVX rats were treated with Veh or human OPG-Fc (10 mg/kg, 2/wk). Serum RANKL and TRACP5b was measured by ELISA. BMD of lumbar vertebrae (L1,L5) and distal femur was measured by DXA. Right distal femurs were processed for bone histomorphometry. Left femurs and the fifth lumbar vertebra (L5) were analyzed by ,CT and biomechanical testing, and L6 was analyzed for ash weight. Results: OVX was associated with significantly greater serum RANKL and osteoclast surface and with reduced areal and volumetric BMD. OPG markedly reduced osteoclast surface and serum TRACP5b while completely preventing OVX-associated bone loss in the lumbar vertebrae, distal femur, and femur neck. Vertebrae from OPG-treated rats had increased dry and ash weight, with no significant differences in tissue mineralization versus OVX controls. ,CT showed that trabecular compartments in OVX-OPG rats had significantly greater bone volume fraction, vBMD, bone area, trabecular thickness, and number, whereas their cortical compartments had significantly greater bone area (p < 0.05 versus OVX-Veh). OPG improved cortical area in L5 and the femur neck to levels that were significantly greater than OVX or sham controls (p < 0.05). Biomechanical testing of L5 and femur necks showed significantly greater maximum load values in the OVX-OPG group (p < 0.05 versus OVX-Veh). Bone strength at both sites was linearly correlated with total bone area (r2 = 0.54,0.74, p < 0.0001), which was also significantly increased by OPG (p < 0.05 versus OVX). Conclusions: OPG treatment prevented bone loss, preserved trabecular architecture, and increased cortical area and bone strength in OVX rats. [source] Thyroid-Stimulating Hormone Restores Bone Volume, Microarchitecture, and Strength in Aged Ovariectomized Rats*,,§JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007T Kuber Sampath PhD Abstract We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. Introduction: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. Materials and Methods: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8,16 wk. Long bones were subjected to ,CT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. Results: In the prevention mode, low doses (0.1 and 0.3 ,g) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 ,g TSH had increased BMD (10,11%), trabecular bone volume (100,130%), trabecular number (25,40%), trabecular thickness (45,60%), cortical thickness (5,16%), mineral apposition and bone formation rate (200,300%), and enhanced mechanical strength of the femur (51,60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. Conclusions: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling. [source] A Nonprostanoid EP4 Receptor Selective Prostaglandin E2 Agonist Restores Bone Mass and Strength in Aged, Ovariectomized RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2006Hua Zhu Ke MD Abstract CP432 is a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 agonist. CP432 stimulates trabecular and cortical bone formation and restores bone mass and bone strength in aged ovariectomized rats with established osteopenia. Introduction: The purpose of this study was to determine whether a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 (PGE2) agonist, CP432, could produce bone anabolic effects in aged, ovariectomized (OVX) rats with established osteopenia. Materials and Methods: CP432 at 0.3, 1, or 3 mg/kg/day was given for 6 weeks by subcutaneous injection to 12-month-old rats that had been OVX for 8.5 months. The effects on bone mass, bone formation, bone resorption, and bone strength were determined. Results: Total femoral BMD increased significantly in OVX rats treated with CP432 at all doses. CP432 completely restored trabecular bone volume of the third lumbar vertebral body accompanied with a dose-dependent decrease in osteoclast number and osteoclast surface and a dose-dependent increase in mineralizing surface, mineral apposition rate, and bone formation rate-tissue reference in OVX rats. CP432 at 1 and 3 mg/kg/day significantly increased total tissue area, cortical bone area, and periosteal and endocortical bone formation in the tibial shafts compared with both sham and OVX controls. CP432 at all doses significantly and dose-dependently increased ultimate strength in the fifth lumber vertebral body compared with both sham and OVX controls. At 1 and 3 mg/kg/day, CP432 significantly increased maximal load in a three-point bending test of femoral shaft compared with both sham and OVX controls. Conclusions: CP432 completely restored trabecular and cortical bone mass and strength in established osteopenic, aged OVX rats by stimulating bone formation and inhibiting bone resorption on trabecular and cortical surfaces. [source] An Uncoupling Agent Containing Strontium Prevents Bone Loss by Depressing Bone Resorption and Maintaining Bone Formation in Estrogen-Deficient RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2005Pierre J. Marie Ph.D. Trabecular bone loss in estrogen deficiency is associated with enhanced bone resorption with a smaller increase in bone formation. We previously reported that low doses of strontium can increase trabecular bone volume in rodents by affecting bone resorption and formation. In this study we determined the effect of a new divalent strontium salt (S12911) on bone loss induced by E2 deficiency. Sprague-Dawley female rats (230 g, n = 15,25 per group) were sham operated or ovariectomized (OVX) and treated with 17,-estradiol (E2, 10 ,g/kg/day, sc) or S12911 by gavage at the dose of 77, 154, or 308 mg/kg/day or the vehicle. Treatment for 60 days with S12911 resulted in a dose-dependent increase in plasma, urine, and bone strontium concentrations without any deleterious effect on total or skeletal growth. OVX rats were osteopenic compared to sham rats as shown by decreased femoral dry bone weight and mineral content measured on bone ash and by DXA. Treatment of OVX rats with S12911 prevented bone loss as bone ash and bone mineral content were restored to the values in sham rats. Trabecular bone volume measured by histomorphometry on the tibial metaphysis was decreased by 46% in OVX rats and was corrected by E2. Treatment of OVX rats with S12911 increased the trabecular bone volume by 30,36%. Histomorphometric indices of bone resorption (osteoclast surface and number) were increased in OVX rats and were reduced by S12911 to the levels in sham rats. In contrast to this inhibitory effect on bone resorption, the osteoid surface, osteoblast surface, mineral apposition rate, and bone formation rate were as high in OVX rats treated with S12911 as in untreated OVX rats. In addition, plasma osteocalcin (OC) and alkaline phosphatase (ALP) levels remained elevated or were further increased in OVX rats treated with S12911. In contrast, treatment with E2 reduced both bone resorption and formation and plasma ALP and OC to the levels in sham rats. The data indicate that the divalent strontium salt S12911 is acting as an uncoupling agent that can prevent the femoral osteopenia and partially prevent the trabecular bone loss in E2-deficient rats by inhibiting bone resorption without reducing bone formation. [source] Long-Term Sensitivity of Uterus and Hypothalamus/Pituitary Axis to 17,-Estradiol Is Higher Than That of Bone in Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2004Reinhold G Erben MD Abstract We examined the long-term sensitivity of uterus and bone to low-dose 17,-estradiol in a 4-month experiment in OVX rats and found that a dose of estradiol that fully protected against uterine atrophy did not protect against bone loss. Our results suggest higher estrogen sensitivity of the uterus compared with bone. Introduction: Estrogen is essential for the function of reproductive tissues and for the normal acquisition and maintenance of bone mass in females. This study was designed to examine the long-term sensitivity of the uterus and bone to low-dose estrogen. Materials and Methods: In preliminary experiments, we determined the lowest subcutaneous dose of 17,-estradiol able to fully protect against uterine atrophy in ovariectomized (OVX) rats. This dose was found to be 1.5 ,g/kg, given five times per week. Subsequently, groups of sham-operated (SHAM) or OVX 6-month-old rats (n = 8 each) were subcutaneously injected with vehicle or 1.5 ,g/kg 17,-estradiol five times per week. All animals were killed 4 months after surgery. Serum osteocalcin and urinary deoxypyridinoline were measured as biochemical markers of bone turnover. Bones were analyzed by bone histomorphometry and pQCT. Results and Conclusions: Our study clearly showed that a dose of estradiol that restores physiological estradiol serum levels, fully maintains uterine weight in OVX rats at the SHAM control level, and suppresses serum follicle-stimulating hormone (FSH) by 67% relative to OVX vehicle controls does not provide significant protection against OVX-induced bone loss at different cancellous and cortical bone sites. We conclude that the long-term sensitivity of the uterus and the hypothalamus/pituitary axis to 17,-estradiol is higher than that of bone in rats. [source] Tower Climbing Exercise Started 3 Months After Ovariectomy Recovers Bone Strength of the Femur and Lumbar Vertebrae in Aged Osteopenic Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2003Takuya Notomi Abstract To determine both the preventive and recovery effects of tower climbing exercise on mass, strength, and local turnover of bone in ovariectomized (OVX) rats, we carried out two experiments. In experiment I, 60 Sprague-Dawley rats, 12 months of age, were assigned to four groups: a Baseline Control, Sham-Operated Sedentary, OVX-Sedentary and OVX-Exercise rats. Rats voluntarily climbed a 200-cm tower to drink water from a bottle set at the top. At 3 months, OVX elevated both the femoral cortex and lumbar trabecular turnover, leading to a reduction in bone mass and strength. However, in OVX-Exercise rats, those values were maintained at the same level as in the Sham-Sedentary rats. Thus, the climbing exercise, started after 3 days of OVX, prevented OVX-induced cortical and trabecular bone loss by depressing turnover elevation. After confirming the preventive effect, we evaluated the recovery effect of exercise. In experiment II, 90 Sprague-Dawley rats, 12 months of age, were assigned to six groups: a Baseline control, two groups of Sham-Operated Sedentary and OVX-Sedentary, and OVX-Exercise rats. The exercise started 3 months after the OVX operation. At 3 months, OVX increased the trabecular bone formation rate and osteoclast surface, leading to a decrease in compressive strength. In the midfemur, the cross-sectional area, moment of inertia, and bending load values decreased. At 6 months, in the OVX-Exercise rats, the parameters of breaking load in both the lumbar and midfemur, lumbar bone mass, and the total cross-sectional area recovered to the same levels as those in the Sham-Sedentary rats. However, the cortical bone area did not recover. Periosteal bone formation increased, while endosteal bone formation decreased. These results showed that the climbing exercise had both a preventive and recovery effect on bone strength in OVX rats. In the mid-femur, effects on bone formation were site-specific, and the cross-sectional morphology was improved without an increase in cortical bone area, supporting cortical drift by mechanical stimulation. [source] Long-Term Dosing of Arzoxifene Lowers Cholesterol, Reduces Bone Turnover, and Preserves Bone Quality in Ovariectomized Rats,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2002Yanfei L. Ma M.D. Abstract Long-term effects of a new selective estrogen receptor modulator (SERM) arzoxifene were examined in ovariectomized (OVX) rats. Arzoxifene was administered postoperatively (po) at 0.1 mg/kg per day or 0.5 mg/kg per day to 4-month-old rats, starting 1 week after OVX for 12 months. At study termination, body weights for arzoxifene groups were 16,17% lower than OVX control, which was caused by mainly reduced gain of fat mass. Longitudinal analysis of the proximal tibial metaphysis (PTM) by computed tomography (CT) at 0, 2, 4, 6, 9, and 12 months showed that OVX induced a 22% reduction in bone mineral density (BMD) at 2 months, which narrowed to a 12% difference between sham-operated (sham) and OVX rats by 12 months. Both doses of arzoxifene prevented the OVX-induced decline in BMD. Histomorphometry of the PTM showed that arzoxifene prevented bone loss by reducing osteoclast number in OVX rats. Arzoxifene maintained bone formation indices at sham levels and preserved trabecular number above OVX controls. Micro-CT analysis of lumbar vertebrae showed similar preservation of BMD compared with OVX, which were not different from sham. Compression testing of the vertebra and three-point bending testing of femoral shaft showed that strength and toughness were higher for arzoxifene-treated animals compared with OVX animals. Arzoxifene reduced serum cholesterol by 44,59% compared with OVX. Uteri wet weight from arzoxifene animals was 38,40% of sham compared with OVX rats, which were 29% of sham. Histology of the uterine endometrium showed that cell heights from both doses of arzoxifene were not significantly different from OVX controls. In summary, treatment of OVX rats with arzoxifene for nearly one-half of a lifetime maintained beneficial effects on cholesterol and the skeleton. These data suggest that arzoxifene may be a useful therapeutic agent for osteoporosis in postmenopausal women. [source] Tibolone Exerts Its Protective Effect on Trabecular Bone Loss Through the Estrogen ReceptorJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2001A. G. H. Ederveen Abstract Tibolone (Org OD14) has estrogenic, progestogenic, and/or androgenic activity depending on the tissue. In postmenopausal women, tibolone prevents bone loss without stimulating the endometrium. Tibolone is effective in preventing trabecular bone loss from the peripheral and axial skeleton of young and old ovariectomized (OVX) rats by reducing bone turnover, that is, bone resorption, like estrogens. We evaluated the contribution of the various hormonal activities to tibolone's bone-conserving effect. Three-month-old OVX rats received tibolone (125 ,g/rat or 500 ,g/rat, twice daily), alone or combined with an antiestrogen, antiandrogen, or antiprogestogen, and the effects on trabecular bone mass and bone turnover were evaluated. Sham-operated and control OVX groups were treated with vehicle. The remaining OVX groups received oral doses of tibolone twice daily, alone or with twice daily (a) antiestrogen ICI 164.384, (b) antiandrogen flutamide, or (c) antiprogestogen Org 31710. For comparison, the effects of 17,-estradiol and testosterone were examined also. After 4 weeks, trabecular bone mineral density (BMD) in the distal femur, plasma osteocalcin, and urinary deoxypyridinoline/creatinine ratio (Dpyr/Cr) were measured. Tibolone or 17,-estradiol significantly blocked ovariectomy-induced loss of trabecular BMD and inhibited bone resorption and bone turnover as judged by reduced Dpyr/Cr ratio and osteocalcin, respectively. These effects of both compounds were counteracted by the antiestrogen. This suggests a major involvement of the estrogen receptor in the action of tibolone on bone metabolism. However, the antiandrogen and the antiprogestogen did not counteract the effects of tibolone, excluding a major role of the androgenic and progestogenic activities of tibolone in its action against trabecular bone loss. The results indicate that tibolone acts on bone almost entirely through activation of the estrogen receptor. [source] Cloning, Sequencing, and Functional Characterization of the Rat Homologue of Receptor Activator of NF-,B Ligand,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2000Jiake Xu Abstract A complementary DNA (cDNA) encoding the rat homologue of receptor activator of NF-,B ligand/osteoprotegerin ligand/osteoclast differentiation factor/tumor necrosis factor (TNF)-related activation-induced cytokine (RANKL/OPGL/ODF/TRANCE) was cloned and sequenced from tibias of ovariectomized (OVX) rats. The predicted amino acid sequence of rat RANKL (rRANKL) has 84% and 96% identity to that of human and mouse RANKL, respectively, and 35% and 37% similarity to that of human and mouse TNF-related apoptosis-inducing ligand (TRAIL), respectively. RANKL transcripts were expressed abundantly in the thymus and bone tissues of OVX rats. rRANKL has a single hydrophobic region between residues 53 and 69, which is most likely to serve as a transmembrane domain. The long C-terminal region containing ,-sheet-forming sequences of the TNF-like core is considered the extracellular region. Three truncated domains within the TNF-like core region were expressed as glutathione S-transferase (GST) fusion proteins and investigated for their ability to induce osteoclastogenesis. The results showed that GST-rRANKL (aa160-318) containing the full TNF-like core region had the highest capability to induce the formation of osteoclast-like cells from RAW264.7 cells. GST-rRANKL (aa239-318 and aa160-268) had lesser degrees of osteoclast inductivity. Furthermore, the GST-rRANKL (aa160-318) is capable of (1) inducing osteoclast formation from rat spleen cells in the presence of macrophage colony-stimulating factor (M-CSF), (2) stimulating mature rat osteoclast polarization and bone resorption ex vivo, and (3) inducing systemic hypercalcemia in vivo; thus the full TNF-like core region of rRANKL is an important regulator of calcium homeostasis and osteoclastic function. [source] Rutin Inhibits Ovariectomy-Induced Osteopenia in RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2000Marie-Noëlle Horcajada-Molteni Abstract Several studies suggest that polyphenols might exert a protective effect against osteopenia. The present experiment was conducted to observe the effects of rutin (quercetin-3- O -glucose rhamnose) on bone metabolism in ovariectomized (OVX) rats. Thirty 3-month-old Wistar rats were used. Twenty were OVX while the 10 controls were sham-operated (SH). Among the 20 OVX, for 90 days after surgery 10 were fed the same synthetic diet as the SH or OVX ones, but 0. 25% rutin (OVX + R) was added. At necropsy, the decrease in uterine weight was not different in OVX and OVX + R rats. Ovariectomy also induced a significant decrease in both total and distal metaphyseal femoral mineral density, which was prevented by rutin consumption. Moreover, femoral failure load, which was not different in OVX and SH rats, was even higher in OVX + R rats than in OVX or SH rats. In the same way, on day 90, both urinary deoxypyridinoline (DPD) excretion (a marker for bone resorption) and calciuria were higher in OVX rats than in OVX + R or SH rats. Simultaneously, plasma osteocalcin (OC) concentration (a marker for osteoblastic activity) was higher in OVX + R rats than in SH rats. High-performance liquid chromatography (HPLC) profiles of plasma samples from OVX + R rats revealed that mean plasma concentration of active metabolites (quercetin and isorhamnetin) from rutin was 9.46 + 1 ,M, whereas it was undetectable in SH and OVX rats. These results indicate that rutin (and/or its metabolites), which appeared devoid of any uterotrophic activity, inhibits ovariectomy-induced trabecular bone loss in rats, both by slowing down resorption and increasing osteoblastic activity. [source] Noradrenaline Involvement in the Negative-Feedback Effects of Ovarian Steroids on Luteinising Hormone SecretionJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2009C. V. V. Helena Noradrenaline has been shown to modulate the ovarian-steroid feedback on luteinising-hormone (LH) release. However, despite the high amount of evidence accumulated over many years, the role of noradrenaline in LH regulation is still not clearly understood. The present study aimed to further investigate the involvement of noradrenaline in the negative-feedback effect of oestradiol and progesterone on basal LH secretion. In experiment 1, ovariectomised (OVX) rats received a single injection of oil, oestradiol, or progesterone at 09.00,10.00 h and were decapitated 30 or 60 min later. Levels of noradrenaline and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were determined in microdissections of the preoptic area (POA) and medial basal hypothalamus-median eminence (MBH-ME) and correlated with LH secretion. Basal LH levels were decreased 30 and 60 min after oestradiol or progesterone injection, and this hormonal response was significantly correlated with a reduction in POA MHPG levels, which reflect noradrenaline release. In addition, noradrenaline levels in the POA were increased, whereas noradrenaline turnover (MHPG/noradrenaline ratio) was decreased 60 min after the injection of both hormones. No effect was found in the MBH-ME. In experiment 2, i.c.v. administration of noradrenaline (60 nmol), performed 15 min before oestradiol or progesterone injection in jugular vein-cannulated OVX rats, completely prevented the ovarian steroid-induced inhibition of LH secretion. The data obtained provide direct evidence that LH secretion in OVX rats is positively regulated by basal noradrenergic activity in the POA, and its reduction appears to play a role in the negative-feedback effect of ovarian steroids on LH secretion in vivo. [source] Possible Role of Oestrogen in Pubertal Increase of Kiss1/Kisspeptin Expression in Discrete Hypothalamic Areas of Female RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2009K. Takase Kisspeptin, a peptide encoded by the Kiss1 gene, has been considered as a potential candidate for a factor triggering the onset of puberty, and its expression in the hypothalamus was found to increase during peripubertal period in rodent models. The present study aimed to clarify the oestrogenic regulation of peripubertal changes in Kiss1 mRNA expression in the anteroventral periventricular nucleus (AVPV) and hypothalamic arcuate nucleus (ARC), and to determine which population of kisspeptin neurones shows a change in kisspeptin expression parallel to that in luteinising hormone (LH) pulses at the peripubertal period. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry revealed an apparent increase in the ARC Kiss1 mRNA expression and kisspeptin immunoreactivity around the time of vaginal opening in intact female rats. The AVPV Kiss1 mRNA levels also increased at day 26, but decreased at day 31, and then increased at day 36/41. In ovariectomised (OVX) rats, ARC Kiss1 mRNA expression did not show peripubertal changes and was kept at a high level throughout peripubertal periods. Apparent LH pulses were found in these prepubertal OVX rats. Oestradiol replacement suppressed ARC Kiss1 mRNA expression in OVX prepubertal rats, but not in adults. Similarly, LH pulses were suppressed by oestradiol in the prepubertal period (days 21 and 26), but regular pulses were found in adulthood. The present study suggests that a pubertal increase of Kiss1/kisspeptin expression both in the ARC and AVPV is involved in the onset of puberty. These results also suggest that both LH pulses and ARC Kiss1 expression are more negatively regulated by oestrogen in prepubertal female rats compared to adult rats. [source] KiSS-1 and GPR54 Genes are Co-Expressed in Rat Gonadotrophs and Differentially Regulated In Vivo by Oestradiol and Gonadotrophin-Releasing HormoneJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2008N. Richard Kisspeptin, the product derived from KiSS-1, and its cognate receptor, GPR54, both exert a role in the neuroendocrine control of reproduction by regulating gonadotrophin-releasing hormone (GnRH) secretion. In the present study, we demonstrate, using dual immunofluorescence with specific antibodies, that the KiSS-1 and GPR54 genes are both expressed in rat gonadotrophs. All luteinising hormone ,-immunoreactive (LH,-ir) cells were stained by the KiSS-1 antibody but some kisspeptin-ir cells were not LH, positive; thus, we cannot exclude the possibility that kisspeptins are expressed in other pituitary cells. All GPR54-ir are co-localised with LH, cells, but only a subset of LH, cells are stained with the GPR54 antibody. Using the real-time reverse transcription-polymerase chain reaction (RT-PCR), we found that the expression of KiSS-1 and GPR54 is differentially regulated by steroids. In the female, KiSS-1 mRNA levels dramatically decreased following ovariectomy (OVX), and this decrease was prevented by administration of 17,-oestradiol (E2), but not by administration of GnRH antagonist or agonist. Administration of E2 in OVX rats receiving either GnRH antagonist or agonist clearly shows that E2 acts directly on the pituitary to positively control KiSS-1 expression. In OVX rats, administration of the selective oestrogen receptor (ER), ligand propylpyrazoletriol, but not the selective ER, ligand diarylpropionitrile, mimics this effect. By contrast, our study shows that GPR54 expression is positively regulated by GnRH and negatively controlled by chronic exposure to E2. In summary, our data document for the first time that, in the female rat pituitary, KiSS-1 expression is up-regulated by oestradiol, similarly to that seen in the anteroventral periventricular nucleus of the hypothalamus. Conversely, GPR54 is up-regulated by GnRH, which exclusively targets gonadotrophs. [source] Increased Caloric Intake on a Fat-Rich Diet: Role of Ovarian Steroids and Galanin in the Medial Preoptic and Paraventricular Nuclei and Anterior Pituitary of Female RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2007S. F. Leibowitz Previous studies in male rats have demonstrated that the orexigenic peptide galanin (GAL), in neurones of the anterior parvocellular region of the paraventricular nucleus (aPVN) projecting to the median eminence (ME), is stimulated by consumption of a high-fat diet and may have a role in the hyperphagia induced by fat. In addition to confirming this relationship in female rats and distinguishing the aPVN-ME from other hypothalamic areas, the present study identified two additional extra-hypothalamic sites where GAL is stimulated by dietary fat in females but not males. These sites were the medial preoptic nucleus (MPN), located immediately rostral to the aPVN, and the anterior pituitary (AP). The involvement of ovarian steroids, oestradiol (E2) and progesterone (PROG), in this phenomenon was suggested by an observed increase in circulating levels of these hormones and GAL in MPN and AP with fat consumption and an attenuation of this effect on GAL in ovariectomised (OVX) rats. Furthermore, in the same four areas affected by dietary fat, levels of GAL mRNA and peptide immunoreactivity were stimulated by E2 and further by PROG replacement in E2 -primed OVX rats and were higher in females compared to males. Because both GAL and PROG stimulate feeding, their increase on a fat-rich diet may have functional consequences in females, possibly contributing to the increased caloric intake induced by dietary fat. This is supported by the findings that PROG administration in E2 -primed OVX rats reverses the inhibitory effect of E2 on total caloric intake while increasing voluntary fat ingestion, and that female rats with higher GAL exhibit increased preference for fat compared to males. Thus, ovarian steroids may function together with GAL in a neurocircuit, involving the MPN, aPVN, ME and AP, which coordinate feeding behaviour with reproductive function to promote consumption of a fat-rich diet at times of increased energy demand. [source] ,1 Adrenoreceptors Mediate The Stimulatory Effects of Oestrogen On Stress-Related Hypothalamic-Pituitary-Adrenal Activity in The Female RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2004V. Viau Abstract Variation in challenge-induced adrenocorticotropin hormone (ACTH) release over the oestrous cycle occurs in response to fluctuations in circulating concentrations of oestrogen and progesterone. However, how these ovarian steroids interact to regulate the principal ACTH cosecretagogues, corticotropin-releasing hormone (CRH) and arginine vasopressin is not understood. Here, we measured median eminence CRH and vasopressin content in intact cycling female rats, and in ovariectomized (OVX) females steroid-replaced in a manner that approximates the relative release patterns of oestrogen and progesterone seen over the oestrous cycle. Intact cycling females showed significantly higher median eminence CRH and vasopressin concentrations during proestrous and oestrous compared to the diestrous phase. In OVX rats, a single 10 µg injection of oestrogen failed to mimic this increase in median eminence CRH and vasopressin. However, this dose significantly elevated CRH and vasopressin content in OVX rats previously exposed to diestrous concentrations of oestrogen and progesterone. Moreover, oestrogen priming enhanced restraint-induced depletion of CRH and vasopressin from the median eminence, but only against a background of low oestrogen and progesterone replacement. Oestrogen-induced elevations in median eminence vasopressin (but not CRH) content were reduced by peripheral administration of the ,1 adrenoreceptor antagonist prazosin. Finally, plasma ACTH concentrations following central injection of the ,1 receptor agonist, phenylephrine, were significantly higher in rats during proestrous compared to diestrous. These results indicate that the stimulatory effect of oestrogen on both the expression and stress-induced release of ACTH cosecretagogues is exerted only against a background of low oestrogen and progesterone levels, and is mediated, in part, via the ,1 adrenoreceptor. [source] Targeted Cytotoxic Analogue of Luteinizing Hormone-Releasing Hormone (LH-RH) Only Transiently Decreases the Gene Expression of Pituitary Receptors for LH-RHJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2002M. Kovacs Abstract A cytotoxic analogue of LH-RH, AN-207, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to carrier [D-Lys6]LH-RH, was developed for targeted therapy of cancers expressing LH-RH-receptors. To determine its possible side-effects on the pituitary gland, we investigated the gene expression of pituitary LH-RH-receptors and LH secretion in ovariectomized female and normal male rats after treatment with the maximum tolerated dose of AN-207. The effect of AN-207 on the gene expression of the pituitary GH-RH-receptors and GH secretion was also assessed in male rats. Five hours after a single i.v. injection of AN-207 at 175 nmol/kg, there was a 39,51% decrease in mRNA expression for the pituitary LH-RH-receptors in male and female rats. The carrier, at an equimolar dose, caused a similar reduction (37,39%), whereas the cytotoxic radical AN-201, at an equitoxic dose (110 nmol/kg), produced only a 12,24% decrease (NS) in the mRNA expression of LH-RH-receptors. AN-207 and the carrier analogue induced a comparable 90,100-fold increase in serum LH concentrations in male rats, and the same 12-fold elevation in OVX rats at 5 h. Seven days after treatment with AN-207, the mRNA levels for the LH-RH receptors and the serum LH concentration were back to normal in both sexes. AN-207, the carrier, and AN-201 had no significant effect on the expression of mRNA for GH-RH-receptors in the pituitary. In vitro, a continuous perfusion of pituitary cells with 10 nM AN-207 did not affect the hormone-releasing function of the targeted LH cells or the nontargeted GH cells. Our results demonstrate that cytotoxic LH-RH analogue AN-207, at the maximum tolerated dose causes only a transient decrease in the gene expression of the pituitary LH-RH receptors, and the levels of mRNA for LH-RH receptor fully recover within 7 days. Moreover, the carrier hormone moiety, and not the cytotoxic radical in AN-207 is responsible for this transient suppression. Our findings suggest that the therapy with cytotoxic LH-RH analogues will not inflict permanent damage to pituitary function. [source] Masculinizing Effect of Dihydrotestosterone on Growth Hormone Secretion is Inhibited in Ovariectomized Rats with Anterolateral Deafferentation of the Medial Basal Hypothalamus or in Intact Female RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2000Tamura There is a striking sex difference in the pattern of growth hormone (GH) secretion in rats. Our previous studies showed that short-term administration of pharmacological doses of testosterone or dihydrotestosterone (DHT) masculinized the GH secretory pattern in ovariectomized (OVX) rats. The locus where testosterone or DHT interacts with the somatotropic axis is believed to be the hypothalamus. To obtain insights into this phenomenon, we administered a single dose of DHT s.c. to adult OVX rats at 0.01, 0.1 or 1 mg/rat. Blood GH concentrations were measured in unanaesthetized rats. Six to12 h after the s.c. administration of all three doses of DHT, the GH secretory pattern revealed a male-like secretory pattern as shown by episodic bursts occurring at 2,3-h intervals with low or undetectable trough levels. When anterolateral deafferentation of the medial basal hypothalamus (ALC) was performed, the blood concentrations revealed irregularly occurring small fluctuations, instead of the usual high bursts, but the basal GH concentration was significantly higher than that of OVX-sham-operated rats. DHT treatment did not elicit pulsatile GH secretion or alter GH concentrations in OVX rats with ALC. When intact adult female rats received DHT at a dose of 1 mg/rat, the male-like GH secretory pattern was not induced. These results suggest that neural inputs from the anterolateral direction to the medial basal hypothalamus are necessary for the masculinizing effect of DHT on the GH secretory pattern in OVX rats, and that oestrogen in intact female rats prevents the masculinizing effect of DHT. [source] The management of menopause with complementary and alternative medicine using an experimental model: Ovariectomized ratsJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2010Suely R. Bello Abstract Aim:, The purpose of this research was to assess the effects of the flower essences She Oak and Bush Fuchsia on behavioral anxiety in ovariectomized (OVX) rats. Methods:, For four weeks, OVX rats received the flower essences She Oak, Bush Fuchsia or a combination of the two. After flower therapy, the animals were subjected to an elevated plus maze (EPM) behavioral anxiety-test. Cortisol blood level was also evaluated. Results:, OVX rats treated with the flower essence She Oak became less anxious and had more entries in the EPM open arms. On the other hand, OVX rats treated with the Bush Fuchsia essence spent more time in the EPM closed arms. This finding is similar to those obtained with controls. In addition, OVX rats that received She Oak and Bush Fuchsia in combination presented the same results as those receiving the Bush Fuchsia alone. Conclusions:, Our results suggest that the flower essence She Oak could have an anxiolytic effect in OVX rats, but that the combination therapy of the She Oak and Bush Fuchsia could avoid the effects of the She Oak. [source] In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2010Songlin Peng Abstract In vitro studies have demonstrated that strontium (Sr) could increase osteogenic differentiation of bone marrow stromal cells (BMSCs). We investigated the in vivo effect of Sr on BMSCs. Thirty-six female rats were randomly divided into the following groups: sham operated and treated with either vehicle (Sham,+,Veh) or Sr compound (Sham,+,Sr) and ovariectomized and treated with either vehicle (OVX,+,Veh) or Sr compound (OVX,+,Sr). Vehicle and Sr were orally administrated daily starting immediately after the surgery and continuing for 12 weeks. The anabolic effect of Sr on trabecular bone was determined at the structural and tissue level by microCT and histomorphometry, respectively. Colony formation assays demonstrated that BMSCs exhibited higher osteogenic colony but lower adipogenic colony in Sr-treated versus Veh-treated OVX rats. The mRNA level of osteogenic genes was higher, while the mRNA level of adipogenic genes was lower in BMSCs from Sr-treated versus Veh-treated Sham and OVX rats. The effect of Sr on rat BMSCs was reproducible in human BMSCs. Taken together, this study suggests that the anabolic effect of Sr on normal or osteoporotic bones is associated with increased osteoblastic differentiation of BMSCs. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1208,1214, 2010 [source] Effects of h-PTH on cancellous bone mass, connectivity, and bone strength in ovariectomized rats with and without sciatic-neurectomyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2004Y. Kasukawa Abstract The purpose of this study was to determine whether h-PTH (1-34) treatment would recover cancellous bone connectivity and bone strength in ovariectomized (OVX) or ovariectomized and sciatic-neurectomized (OVX + NX) rats. Seven-month-old female Wistar rats were treated with h-PTH or vehicle (6.0 ,g/kg, six times a week, subcutaneously) for four weeks beginning 4, 8, or 12 weeks after OVX or OVX + NX. These were compared to age-matched baseline and sham-operated groups. Right tibiae were used for bone histomorphometry and node-strut analysis, and left tibiae were used for mechanical testing. The bone formation rates in the OVX and OVX + NX rats treated with h-PTH were significantly higher than those in their baseline controls, h-PTH treatment increased the node numbers and failure energies in the OVX rats, compared to their baseline controls, at all time points. However, in the OVX + NX rats, the effects of h-PTH treatment on the node number and failure energy were observed only at four weeks after surgery, but not at eight weeks or 12 weeks after surgery. These results suggest that the lowest limit, at which trabecular connectivity and bone strength are able to be restored by h-PTH, occurred between four and eight weeks in OVX + NX rats, but not in OVX rats, h-PTH cannot recover trabecular connectivity and bone strength in advanced osteopenia. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Efficacy of the injectable calcium phosphate ceramics suspensions containing magnesium, zinc and fluoride on the bone mineral deficiency in ovariectomized ratsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Makoto Otsuka Abstract The purpose of this study was to evaluate the therapeutic efficacy of a new calcium phosphate (CaP)-based formulation in improving the bone mineral deficiency in ovariectomized (OVX) rats. The ions release experiments for CaP preparations (G2: 0.46% Mg, 5.78% Zn, and 2.5% F; G3:3.1% Mg, 0.03% Zn, and 3.01% F; G4: 1.25% Mg, 1.77% Zn, 1.35% F) and of a Zn-TCP (G1: 6.17% Zn) powders, the initial Mg and Zn ion release rates of MZF-CaPs were performed in acetate buffer at pH 4.5 (37°C). Wistar rats were divided into six groups including a normal (not OVX) group (GN) and a control, OVX group (GC). Rats in groups GC, G1, G2, G3, G4 were OVX. Suspensions consisting of CaP preparations (G2, G3, G4) and of a Zn-TCP (G1) powders were injected in the right thighs of OVX rats in all groups except for GN and GC, once a week for 4 weeks. GN and GC rats were injected with saline solutions. Plasma was analyzed for Zn land alkaline phosphatase levels. The bone mineral density (BMD) was measured using DEXA and the bone (femur) strength determined using three-point-bending analysis. G1 and G2 groups showed high plasma Zn levels. The area under the curve of plasma Zn was significantly greater in the G1, G2, and GN groups than in the G3, G4, and GC groups (p,<,0.05). The BMD and bone mechanical strength of the right femur were significantly higher in the G1, G2, G3, and G4 groups than GC group on day 28. The right femur had significantly greater BMD and bone mechanical strength than the left femur in G1, G2, G3, and G4 groups. However, there was no significant difference in the BMD of the right femur between the G1, G2, G3, and G4 groups. Results indicate that the new injectable CaP formulations are effective in improving bone properties of OVX rats and may be useful in osteoporosis therapy. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:421,432, 2008 [source] Estrogen-Dependent Enhancement of NO Production in the Nucleus Tractus Solitarius Contributes to Ethanol-Induced Hypotension in Conscious Female RatsALCOHOLISM, Issue 2 2009Guichu Li Background:, Our previous pharmacological and cellular studies showed that peripheral (cardiac and vascular) nitric oxide synthase (NOS)-derived NO is implicated in the estrogen (E2)-dependent hypotensive action of ethanol in female rats. The objective of this study was to test the hypothesis that enhanced NO production in the nucleus tractus solitarius (NTS) is implicated in the E2 -dependent hypotensive action of ethanol. Methods:, To achieve this goal, we utilized in vivo electrochemistry to measure real time changes in neuronal NO to investigate the acute effects of intragastric ethanol (0, 0.5, or 1 g/kg) on NO in NTS neurons, blood pressure (BP), and heart rate (HR) in conscious female rats in the absence (ovariectomized, OVX, rats) or presence of E2. Results:, In sham operated (SO) rats, ethanol elicited dose-related increase in NTS NO and reduction in BP. These neurochemical and BP effects of ethanol were absent in OVX rats. Whether the neurochemical effect of ethanol and the associated hypotension are dependent on rapid E2 signaling was investigated. In OVX rats pretreated, 30 minutes earlier, with E2 (1 ,g/kg), intragastric ethanol (1 g/kg) increased NTS NO and reduced BP and these responses were comparable to those obtained in SO rats. Conclusions:, The present findings suggest that increased production of NO in NTS neurons contributes to ethanol-evoked hypotension in female rats. Further, ethanol enhancement of neuronal NO production in the brainstem is dependent on rapid E2 signaling. [source] Effects of Estrogen on Postischemic Pial Artery Reactivity to ADPMICROCIRCULATION, Issue 5 2009MIN LI ABSTRACT Objective: The aims of this work were to determine if 1) ischemia alters pial artery responsiveness to the partially nitric oxide (NO)-dependent dilator, ADP, 2) the alteration depends on 17,-estradial (E2), and 3) NO contributes to E2 protective effects. Materials and Methods: Response to ADP and the non-NO-dependent dilator, PGE2, were examined through closed cranial windows. Ovariectomized (OVX) and E2-replaced (E25, 0.025 mg; or E50, 0.05 mg) rats were subjected to 15-minute forebrain ischemia and one-hour reperfusion. Endothelial NO synthase (eNOS) expression was determined in pre- and postischemic isolated cortical microvessels. Results: In OVX rats, ischemia depressed pial responses to ADP, but not to PGE2. Both doses of E2 maintained responses to ADP and had no effect on the response to PGE2. eNOS inhibition decreased the ADP response by 60% in the E25 rats and 50% in the E50 rats, but had no effect in the OVX rats. Compared to the OVX group, microvessel expression of eNOS was increased by E2, but postischemic eNOS was unchanged in both groups. Conclusions: The nearly complete loss of postischemic dilation to ADP suggests that normal non-NO-mediated dilatory mechanisms may be acutely impaired after ischemic injury. Estrogen's protective action on ADP dilation may involve both NO- and non-NO-mediated mechanisms. [source] A hot water extract of Chlorella pyrenoidosa reduces body weight and serum lipids in ovariectomized ratsPHYTOTHERAPY RESEARCH, Issue 2 2004Saburo Hidaka Abstract The effects of a hot water extract of Chlorella pyrenoidosa, which contains chlorella growth factor (CGF), on the body weight, serum lipids, and the bone mass were evaluated using an ovariectomized rat as a model for postmenopausal bone loss. Rats were divided into four groups: sham-operated (Sham), Sham given the CGF solution, ovariectomized (OVX), and OVX given the CGF solution, respectively. Administration of the extract to OVX rats suppressed the body weight gain. After 7 weeks, the administration of the extract to the OVX group reduced increases in both serum total cholesterols and high-density lipoprotein (HDL) cholesterols. It also normalized the decrease of triglyceride level in the OVX group. The ovariectomy decreased the tibial bone mineral density (BMD) by 19%, and the administration of the extract to OVX rats did not inhibit this decrease. These results suggest that a dietary supplement of CGF may be useful to control the body weight and improve lipid metabolism of menopausal women. Copyright © 2004 John Wiley & Sons, Ltd. [source] Evaluation of a soybean product fujiflavone P40 as an antiosteoporotic agent in ratsPHYTOTHERAPY RESEARCH, Issue 2 2003Saburo Hidaka Abstract The preventive effects of Fujiflavone P40 (a soybean isoflavone product) against both bone loss and periodontal alteration were evaluated using an ovariectomized rat model. Rats were divided into five groups: sham-operated (Sham), ovariectomized (OVX), OVX given Fujiflavone P40, OVX given 17,-oestradiol, and OVX given the vehicle for 17,-oestradiol, respectively. Fujiflavone P40 contains 46.6% isoflavones which consist of 24.1% daidzin, 16.5% glycitin and 5.9% genistin. Administration of Fujiflavone P40 to OVX rats suppressed the body weight gain until 5 weeks. Fujiflavone P40 also decreased total and high-density lipoprotein (HDL) cholesterols and triglyceride level of OVX rats, significantly. After 7 weeks, Fujiflavone P40 did not recover the coarsened fibre of the periodontal ligament. The ovariectomy decreased the uterine weight by 78%. The administration of 17, -oestradiol recovered the weight loss by 99%, while Fujiflavone P40 restored it by 33%. The ovariectomy decreased the tibial bone mineral density (BMD) by 22%. The administration of 17,-oestradiol to OVX rats recovered the tibial BMD decrease by 100%, while Fujiflavone P40 recovered it by 78%. The results suggest that Fujiflavone P40 may be useful as a preventive agent for osteoporosis. Copyright © 2003 John Wiley & Sons, Ltd. [source] Bone Affinity of a Bisphosphonate-Conjugated Protein in VivoBIOTECHNOLOGY PROGRESS, Issue 6 2000Hasan Uludag Growth factors capable of stimulating bone formation are potential therapeutic agents for osteoporosis treatment. It is essential, however, that a targeting mechanism is incorporated into the growth factors to deposit them at osseous tissue with minimal distribution to extraskeletal sites. To this end, a strategy has been developed in which a bone-seeking molecule, 1-amino-1,1-diphosphonate methane (aminoBP), was chemically conjugated to a model protein, bovine serum albumin (BSA). This study was carried out to assess the bone affinity of the conjugates in a tibia injection model. Using ovariectomized (OVX) rats, initial (3 h) retention of BSA and aminoBP-BSA were found to be equivalent when injected into the medullary cavity of tibia. After 1 day, an 8- and 12-fold higher tibiae retention of the protein was obtained in normal and OVX rats as a result of aminoBP conjugation. A similar result (,12-fold difference) was also obtained in OVX rats after 3 days. We concluded that aminoBP conjugation to BSA imparted a high bone affinity and enhanced bone retention of proteins in normal and OVX rats. [source] Uterine Adenocarcinoma in N -Ethyl- N -nitro- N -nitrosoguanidine-treated Rats with High-dose Exposure to p-tert-Octylphenol during AdulthoodCANCER SCIENCE, Issue 2 2002Shin-ichi Katsuda Since many risk factors are associated with the development of uterine adenocarcinomas in humans, the etiology is unclear in most cases, although it has been pointed out that estrogen may play essential roles. To clarify the effects of exposure to p-tert-octylphenol (OP), an environmental xenoestrogen, on uterine carcinogenesis, adult Donryu rats were initiated with a single intrauterine treatment of N -ethyl- N -nitro- N -nitrosoguanidine (ENNG) at 11 weeks of age and exposed thereafter to 100 mg/kg OP by s.c. injection until 15 months of age. Adult ovariectomized (OVX) rats were also treated in a similar way. OP had no effect on occurrence of persistent estrus in middle age, although uterotrophic effects were obvious in OVX rats. At the termination, development of uterine adenocarcinomas was significantly increased in animals exposed to OP during adulthood. No tumors, but a few focal hyperplasias, developed in OVX rats. These findings suggest that OP has tumor-promoting effects on ENNG-treated endometrium of rats, possibly due to direct action on the uterus, as indicated by the uterotrophic effect when a high dose of OP was given. The results provide clues to the mechanisms of influence of hormonal disrupters on uterine carcinogenesis. [source] Morphine modulation of temporomandibular joint-responsive units in superficial laminae at the spinomedullary junction in female rats depends on estrogen statusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2008A. Tashiro Abstract The influence of analgesic agents on neurons activated by stimulation of the temporomandibular joint (TMJ) region is not well defined. The spinomedullary junction [trigeminal subnucleus caudalis (Vc)/C1,2] is a major site of termination for TMJ sensory afferents. To determine whether estrogen status influences opioid-induced modulation of TMJ units, the classical opioid analgesic, morphine, was given to ovariectomized (OvX) rats and OvX rats treated for 2 days with low-dose (LE2) or high-dose (HE2) 17,-estradiol-3-benzoate. Under thiopental anesthesia, TMJ units in superficial and deep laminae at the Vc/C1,2 junction were activated by injection of ATP (1 mm) directly into the joint space. In superficial laminae, morphine inhibited evoked activity in units from OvX and LE2 rats in a dose-related and naloxone-reversible manner, whereas units from HE2 rats were not inhibited. By contrast, in deep laminae, morphine reduced TMJ-evoked unit activity similarly in all groups. Morphine reduced the background activity of units in superficial and deep laminae and resting arterial pressure similarly in all groups. Morphine applied to the dorsal surface of the Vc/C1,2 junction inhibited all units independently of E2 treatment. Quantitative polymerase chain reaction and immunoblots revealed a similar level of expression for ,-opioid receptors at the Vc/C1,2 junction in LE2 and HE2 rats. These results indicated that estrogen status differentially affected morphine modulation of TMJ unit activity in superficial, but not deep, laminae at the Vc/C1,2 junction in female rats. The site(s) for estrogen influence on morphine-induced modulation of TMJ unit activity was probably outside the medullary dorsal horn. [source] Daidzein but not other phytoestrogens preserves bone architecture in ovariectomized female rats in vivoJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2008D. Somjen Abstract Ovariectomy of immature female rats, results in significant decrease of trabecular bone volume and in cortical bone thickness. Previously, we found that estradiol-17, (E2) restored bone structure of ovariectomized (Ovx) female rats to values obtained in intact sham-operated female rats. E2 also selectively stimulated creatine kinase (CK) specific activity a hormonal-genomic activity marker. In the present study, we compared the effects of E2 and the phytoestrogens: daidzein (D), biochainin A (BA), genistein (G), carboxy-derivative of BA (cBA), and the SERM raloxifene (Ral) in Ovx, on both histological changes of bones and CK, when administered in multiple daily injections for 2.5 months. Bone from Ovx rats, showed significant disrupted architecture of the growth plate, with fewer proliferative cells and less chondroblasts. The metaphysis underneath the growth plate, contained less trabeculae but a significant increased number of adipocytes in the bone marrow. D like E2 and Ral but not G, BA, or cBA, restored the morphology of the tibiae, similar to that of control sham-operated animals; the bony trabeculeae observed in the primary spongiosa was thicker, with almost no adipocytes in bone marrow. Ovariectomy resulted also in reduced CK, which in both epiphysis and diaphysis was stimulated by all estrogenic compounds tested. In summary, only D stimulated skeletal tissues growth and differentiation as effectively as E2 or Ral, suggesting that under our experimental conditions, D is more effective in reversing menopausal changes than any of the other isolated phytoestrogens which cannot be considered as one entity. J. Cell. Biochem. 103: 1826,1832, 2007. © 2007 Wiley-Liss, Inc. [source] | |||||||||||||