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Ovariectomized Rats (ovariectomized + rat)

Distribution by Scientific Domains

Medical Sciences	68%
Life Sciences	25%
Chemistry	6%

Selected Abstracts

A Vacuolar ATPase Inhibitor, FR167356, Prevents Bone Resorption in Ovariectomized Rats With High Potency and Specificity: Potential for Clinical Application,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005
Kazuaki Niikura MS
Abstract FR167356, a novel inhibitor of vacuolar ATPase, has high potency against osteoclast V-ATPase and low potency against lysosomal V-ATPase. FR167356 is the first compound of this nature to be tested. It has the potential to be useful for clinical application. Introduction: It has been suggested that the key issue regarding the therapeutic usefulness of V-ATPase inhibitors is their selectivity. Materials and Methods: In in vitro and in vivo studies, we compared FR167356 with other vacuolar ATPase (V-ATPase) inhibitors, bafilomycin A1 and SB242784. H+ transport by various membrane vesicles was assayed by measuring uptake of acridine orange. Inhibitory activity against in vitro bone resorption was examined by measuring the Ca2+ release from cultured calvariae. In vivo, hypercalcemia was induced by retinoic acid in thyroparathyroidectomized-ovariectomized rats, and the effect on serum Ca2+ level was assessed. Ovariectomized rats were treated with FR167356 or SB242784. One week after surgery, free deoxypyridinoline levels in 24-h urine samples, which were collected from 6 h after administration of FR167356, were measured by ELISA. After 4 weeks of treatment, plasma biochemical parameters were analyzed. BMD of the distal femur metaphysis was measured with pQCT. Histomorphometric analysis of the proximal tibias was performed. Blood gases of rats treated with FR167356 were measured with a blood gas analyzer for estimating the effect of FR167356 on in vivo function of renal V-ATPase. Results: FR167356, which is distinctly different from other V-ATPase inhibitors, has a high potency against osteoclast V-ATPase and low potency against lysosomal V-ATPase. Similarly, FR167356 inhibited bone resorption in vitro when stimulated by PTH, IL-1, and IL-6. FR167356 reduced retinoic acid-induced hypercalcemia in thyroparathyroidectomized-ovariectomized rats in a dose-dependent manner. Moreover, FR167356 was shown to restore BMD of ovariectomized rats caused by the inhibition of bone resorption. Ovariectomized rats treated with FR167356 did not show adverse symptoms, whereas SB242784 caused a decrease in body weight gain and significant changes in two plasma biochemical parameters. Interestingly, FR167356 treatment did not affect blood acid-base balance; however, FR167356 inhibited renal V-ATPase with a similar potency as for osteoclast V-ATPase inhibition. Conclusion: Comparison of FR167356 with SB242784 implies that the characteristics of FR167356 may be more appropriate for clinical application as a V-ATPase inhibitor. [source]

A hot water extract of Chlorella pyrenoidosa reduces body weight and serum lipids in ovariectomized rats

PHYTOTHERAPY RESEARCH, Issue 2 2004
Saburo 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]

Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus.

DEVELOPMENTAL NEUROBIOLOGY, Issue 9 2006
The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective
Abstract The ovarian hormone progesterone is neuroprotective in different experimental models of neurodegeneration. In the nervous system, progesterone is metabolized to 5,-dihydroprogesterone (DHP) by the enzyme 5,-reductase. DHP is subsequently reduced to 3,,5,-tetrahydroprogesterone (THP) by a reversible reaction catalyzed by the enzyme 3,-hydroxysteroid dehydrogenase. In this study we have analyzed whether progesterone metabolism is involved in the neuroprotective effect of the hormone in the hilus of the hippocampus of ovariectomized rats injected with kainic acid, an experimental model of excitotoxic cell death. Progesterone increased the levels of DHP and THP in plasma and hippocampus and prevented kainic-acid-induced neuronal loss. In contrast to progesterone, the synthetic progestin medroxyprogesterone acetate (MPA, Provera) did not increase DHP and THP levels and did not prevent kainic-acid-induced neuronal loss. The administration of the 5,-reductase inhibitor finasteride prevented the increase in the levels of DHP and THP in plasma and hippocampus as a result of progesterone administration and abolished the neuroprotective effect of progesterone. Both DHP and THP were neuroprotective against kainic acid. However, the administration of indomethacin, a 3,-hydroxysteroid dehydrogenase inhibitor, blocked the neuroprotective effect of both DHP and THP, suggesting that both metabolites are necessary for the neuroprotective effect of progesterone. In conclusion, our findings indicate that progesterone is neuroprotective against kainic acid excitotoxicity in vivo while the synthetic progestin MPA is not and suggest that progesterone metabolism to its reduced derivatives DHP and THP is necessary for the neuroprotective effect of the hormone. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source]

Serotonin mediates oestrogen stimulation of cell proliferation in the adult dentate gyrus

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001
Mounira Banasr
Abstract Characterizing the mechanisms by which endogenous factors stimulate neurogenesis is of special interest in view of the possible implication of newly generated cells in hippocampal functions or disorders. The aim of this study was to determine whether serotonin (5-HT) and oestradiol (E2) act through a common pathway to increase cell proliferation in the adult dentate gyrus (DG). We also investigated the effects of long-lasting changes in oestrogen levels on cell proliferation. Combining ovariectomy with inhibition of 5-HT synthesis using p -chlorophenylalanine (PCPA) treatment produced approximately the same decreases in the number of bromodeoxyuridine (BrdU) and PSA-NCAM immunolabelled cells in the subgranular layer as ovariectomy alone. Administration of 5-hydroxytryptophan (5-HTP) restored cell proliferation primarily decreased by ovariectomy, whereas oestradiol was unable to reverse this change in ovariectomized rats treated with PCPA. These findings demonstrate that 5-HT mediates oestrogen stimulation of cell proliferation in adult dentate gyrus. However, increase in ovarian hormones during pregnancy has no effect on dentate cell proliferation. This finding suggests that concomitant changes in other factors, such as glucocorticoids, may counterbalance the positive regulation of cell proliferation by 5-HT and oestradiol. Finally, oestrogen may regulate structural plasticity by stimulating PSA-NCAM expression independently of neurogenesis, as shown for instance by the increases in the number of PSA-NCAM labelled cells in pregnants. As 5-HT and oestrogen are involved in mood disorders, our data suggest that the positive regulation of cell proliferation and neuroplasticity by these two factors may contribute to restore hippocampal connectivity in depressive patients. [source]

Estrogen is involved in early alcohol-induced liver injury in a rat enteral feeding model

HEPATOLOGY, Issue 1 2000
Ming Yin
The aim of this study was to investigate whether reduction in blood estrogen by removal of the ovaries would decrease the sensitivity of female rats to early alcohol-induced liver injury using an enteral ethanol feeding model, and if so, whether estrogen replacement would compensate. Livers from ovariectomized rats with or without estrogen replacement after 4 weeks of continuous ethanol exposure were compared with nonovariectomized rats in the presence or absence of ethanol. Ethanol increased serum alanine transaminase (ALT) levels from 30 ± 6 to 64 ± 7 U/L. This effect was blocked by ovariectomy (31 ± 7) and totally reversed by estrogen replacement (110 ± 23). Ethanol increased liver weight and fat accumulation, an effect that was minimized by ovariectomy and reversed partially by estrogen replacement. Infiltrating leukocytes were increased 6.7-fold by ethanol, an effect that was blunted significantly by ovariectomy and reversed by estrogen replacement. Likewise, a similar pattern of changes was observed in the number of necrotic hepatocytes. Blood endotoxin and hepatic levels of CD14 messenger RNA (mRNA) and protein were increased by ethanol. This effect was blocked in ovariectomized rats and elevated by estrogen replacement. Moreover, Kupffer cells isolated from ethanol-treated rats with estrogen replacement produced more tumor necrosis factor , (TNF-,) than those from control and ovariectomized rats. It is concluded, therefore, that the sensitivity of rat liver to alcohol-induced injury is directly related to estrogen, which increases endotoxin in the blood and CD14 expression in the liver, leading to increased TNF-, production. [source]

Long-Term Protective Effects of Zoledronic Acid on Cancellous and Cortical Bone in the Ovariectomized Rat,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2008
Jürg A Gasser PhD
Abstract Current bisphosphonate therapies effectively prevent bone loss in postmenopausal women. We studied the effect of a single intravenous dose of ZOL in ovariectomized rats. Protection from bone loss was dose dependent, lasting for up to 32 weeks, supporting the rationale for an annual intravenous dosing regimen of ZOL for treatment of postmenopausal osteoporosis. Introduction: Once-yearly dosing with zoledronic acid (ZOL) 5 mg can increase BMD and reduce fracture rate in postmenopausal women with low BMD. The primary objective of this study was to determine the duration of bone protective effects of a single dose of ZOL in ovariectomized rats, an animal model of postmenopausal osteopenia. Secondary objectives were to determine the effects on bone turnover and mechanical properties. Materials and Methods: Female Wistar rats (10 per group) received single intravenous doses of ZOL 0.8, 4, 20, 100, or 500 ,g/kg, alendronate 200 ,g/kg, or isotonic saline 4 days before bilateral ovariectomy. Sham-operated controls were pretreated with saline. Mass and density of cancellous and cortical bone (pQCT) were measured at 4-wk intervals for 32 wk. Bone architecture (,CT), bone formation dynamics (fluorochrome label-based histomorphometry), and biomechanical strength in compression testing were also assessed at 32 wk. Results: Ovariectomy-associated BMD loss was significantly attenuated for 32 wk by ZOL ,4 ,g/kg for total BMD, ZOL ,20 ,g/kg for cortical BMD, and ZOL ,4 ,g/kg for cancellous BMD (p < 0.01 versus ovariectomized controls). Alendronate 200 ,g/kg was of equivalent potency to ZOL 20 ,g/kg. Ovariectomy-associated decreases in trabecular architectural parameters were dose-dependently attenuated by ZOL. Alendronate 200 ,g/kg was equivalent to ZOL 20 ,g/kg. The bone resorption marker TRACP5b indicated transient suppression of elevated osteoclast activity by ZOL relative to OVX-rats even at the lowest dose of 0.8 ,g/kg, whereas at 100,500 ,g/kg, the effect was significant relative to the OVX control for the entire duration of the study of 32 wk. Bone formation parameters were not significantly affected by ZOL 20 ,g/kg but were significantly reduced by ZOL 100,500 ,g/kg. Alendronate 200 ,g/kg was equivalent to ZOL 100 ,g/kg. ZOL produced dose-related improvements in bone strength parameters after ovariectomy. Alendronate 200 ,g/kg was of similar potency to ZOL 20 ,g/kg. Conclusions: The duration and magnitude of the bone-protecting effect of a single intravenous dose of ZOL in ovariectomized rats is dose dependent and lasts for up to 32 wk. Compared with alendronate, ZOL shows 10-fold higher potency in preventing bone loss. These data support the use of an annual intravenous ZOL dosing regimen for the treatment of osteoporosis. [source]

A Nonprostanoid EP4 Receptor Selective Prostaglandin E2 Agonist Restores Bone Mass and Strength in Aged, Ovariectomized Rats

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2006
Hua 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]

A Vacuolar ATPase Inhibitor, FR167356, Prevents Bone Resorption in Ovariectomized Rats With High Potency and Specificity: Potential for Clinical Application,

Effects of Genistein and Hormone-Replacement Therapy on Bone Loss in Early Postmenopausal Women: A Randomized Double-Blind Placebo-Controlled Study,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2002
Nunziata Morabito
Abstract The natural isoflavone phytoestrogen genistein has been shown to stimulate osteoblastic bone formation, inhibit osteoclastic bone resorption, and prevent bone loss in ovariectomized rats. However, no controlled clinical trial has been performed so far to evaluate the effects of the phytoestrogen on bone loss in postmenopausal women. We performed a randomized double-blind placebo-controlled study to evaluate and compare with hormone-replacement therapy (HRT) the effect of the phytoestrogen genistein on bone metabolism and bone mineral density (BMD) in postmenopausal women. Participants were 90 healthy ambulatory women who were 47,57 years of age, with a BMD at the femoral neck of <0.795 g/cm2. After a 4-week stabilization on a standard fat-reduced diet, participants of the study were randomly assigned to receive continuous HRT for 1 year (n = 30; 1 mg of 17,-estradiol [E2] combined with 0.5 mg of norethisterone acetate), the phytoestrogen genistein (n = 30; 54 mg/day), or placebo (n = 30). Urinary excretion of pyridinoline (PYR) and deoxypyridinoline (DPYR) was not significantly modified by placebo administration either at 6 months or at 12 months. Genistein treatment significantly reduced the excretion of pyridinium cross-links at 6 months (PYR = ,54 ± 10%; DPYR = ,55 ± 13%; p < 0.001) and 12 months (PYR = ,42 ± 12%; DPYR = ,44 ± 16%; p < 0.001). A similar and not statistically different decrease in excretion of pyridinium cross-links was also observed in the postmenopausal women randomized to receive HRT. Placebo administration did not change the serum levels of the bone-specific ALP (B-ALP) and osteocalcin (bone Gla protein [BGP]). In contrast, administration of genistein markedly increased serum B-ALP and BGP either at 6 months (B-ALP = 23 ± 4%; BGP = 29 ± 11%; p < 0.005) or at 12 months (B-ALP = 25 ± 7%; BGP = 37 ± 16%; p < 0.05). Postmenopausal women treated with HRT had, in contrast, decreased serum B-ALP and BGP levels either at 6 months (B-ALP = ,17 ± 6%; BGP = ,20 ± 9%; p < 0.001) or 12 months (B-ALP = ,20 ± 5%; BGP = ,22 ± 10%; p < 0.001). Furthermore, at the end of the experimental period, genistein and HRT significantly increased BMD in the femur (femoral neck: genistein = 3.6 ± 3%, HRT = 2.4 ± 2%, placebo = ,0.65 ± 0.1%, and p < 0.001) and lumbar spine (genistein = 3 ± 2%, HRT = 3.8 ± 2.7%, placebo = ,1.6 ± 0.3%, and p < 0.001). This study confirms the genistein-positive effects on bone loss already observed in the experimental models of osteoporosis and indicates that the phytoestrogen reduces bone resorption and increases bone formation in postmenopausal women. [source]

Effects of estrogen and progesterone treatment on rat hippocampal NMDA receptors: Relationship to Morris water maze performance

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2004
Nahid K. El-Bakri
Abstract Estrogen modulates NMDA receptors function in the brain. It increases both dendritic spine density and synapse number in the hippocampus, an effect that can be blocked by NMDA antagonist. In this study, we investigated the effect of 17,-estradiol and progesterone treatment on NMDA receptors in ovariectomized rats. Two different doses were used for 10 weeks. Receptor autoradiography was done on brain sections using [3H] MK-801 as a ligand. Our results showed a significant increase in [3H] MK-801 binding in the dentate gyrus, CA3 and CA4 areas of the hippocampus of ovariectomized compared to sham operated rats. In addition, we observed similar changes in CA1. 17,-estradiol treatment in both doses reduced the binding back to the normal level while progesterone treatment did not show any effect. Spatial reference memory was tested on Morris water maze task. Ovariectomy severely impaired spatial reference memory. Estradiol but not progesterone treatment significantly improved the memory performance of the ovariectomized rats. Low dose treatment showed better learning than high dose estrogen treatment. The decrease in the antagonist sites by estradiol treatment could result in an increase in the sensitivity of the hippocampus to the excitatory stimulation by glutamate system and hence the effect of estradiol on learning and memory. The changes of NMDA receptors in the hippocampus support the concept that estrogen-enhancing effect on spatial reference memory could be through the enhancing of NMDA function. [source]

Antitumor and Antiangiogenic Activity of Soy Phytoestrogen on 7,12-Dimethylbenz[,]anthracene-Induced Mammary Tumors Following Ovariectomy in Sprague,Dawley Rats

JOURNAL OF FOOD SCIENCE, Issue 7 2009
Xinmei Kang
ABSTRACT:, Soy phytoestrogen is often used as hormone replacement therapy to alleviate the symptoms of menopause in postmenopausal women. Since estrogen has been considered as an important risk factor for the development of breast carcinoma, we need to know whether it is safe for these postmenopausal women with breast cancer to take soy foods that are rich in phytoestrogen. In the present study, we investigated the efficacy of soy phytoestrogen on tumor proliferation, apoptosis, and angiogenesis in mammary tumors that had already formed in ovariectomized rats. We found that soy phytochemical extraction inhibited proliferation and induced apoptosis,in vitro,and,in vivo, and it demonstrated better antitumor effects than single phytoestrogen. Soy phytochemical extraction also produced surprisingly good antiangiogenic effects, which were evidenced by lower microvascular density, reduced plasma vascular endothelial growth factor, and increased plasma endostatin levels. Our findings suggest that soy phytochemical extraction exerts significant antitumor and antiangiogenic activity in a postmenopausal animal model with breast cancer. [source]

Changes in Progesterone Receptor Isoforms Content in the Rat Brain During the Oestrous Cycle and After Oestradiol and Progesterone Treatments

JOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2003
C. Guerra-Araiza
Abstract We studied the effects of oestradiol and progesterone on progesterone receptor (PR) isoform content in the brain of ovariectomized rats and in intact rats during the oestrous cycle by Western blot analysis. In the hypothalamus and the preoptic area of ovariectomized rats, PR-A and PR-B content was increased by oestradiol, whereas progesterone significantly diminished the content of both PR isoforms after 3 h of treatment in the hypothalamus, but not in the preoptic area. In the hippocampus, only PR-A content was significantly increased by oestradiol while progesterone significantly diminished it after 12 h of treatment. In the frontal cortex, no treatment significantly modified PR isoform content. During the oestrous cycle, the lowest content of PR isoforms in the hypothalamus was observed on diestrus day and, by contrast, in the preoptic area, the highest content of both PR isoforms was observed on diestrus day. We observed no changes in PR isoform content in the hippocampus during the oestrous cycle. These results indicate that the expression of PR isoforms is differentially regulated by sex steroid hormones in a regionally specific manner. [source]

Lipopolysaccharide Inhibits Luteinizing Hormone Release Through Interaction with Opioid and Excitatory Amino Acid Inputs to Gonadotropin-Releasing Hormone Neurones in Female Rats: Possible Evidence for a Common Mechanism Involved in Infection and Immobilization Stress

JOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2003
D. He
Abstract Acute immobilization stress suppresses naloxone- and N -methyl- d -aspartate (NMDA)-induced, but not gonadotropin-releasing hormone (GnRH)-induced, luteinizing hormone (LH) release in ovariectomized oestrogen-primed rats. To explore whether a common mechanism may underlie inhibition of gonadotropin secretion by various stressors, we examined in the present study the effect of lipopolysaccharide (LPS) on LH release induced by progesterone, GnRH, naloxone and NMDA. The effect of LPS on Fos expression in GnRH neurones was also examined in association with its effect on steroid-induced LH release. Injection of progesterone (1 mg/rat) at noon induced an LH surge in the afternoon in ovariectomized rats pretreated with oestradiol benzoate. In these rats, the majority of hypothalamic GnRH neurones expressed Fos in the evening. Intravenous (i.v.) administration of LPS (10 µg/rat) inhibited steroid-induced LH release and also reduced the Fos expression in GnRH neurones. In separate experiments, an i.v. injection of GnRH (50 ng/kg), naloxone (10 mg/kg) or NMDA (20 mg/kg) significantly elevated serum LH concentrations within 10 min. Pretreatment with LPS, which did not affect basal LH release or GnRH-induced LH release, inhibited naloxone-induced and NMDA-induced LH release. These results show that LPS has a suprapituitary site(s) of action to suppress the activity of GnRH neurones in female rats, and suggest that LPS affects the opioid, as well as the excitatory amino acidergic regulation of GnRH neurones. The similarity of effects of LPS and immobilization stress further suggests that a common mechanism is involved in inhibition of GnRH neurones by different stressors. [source]

Oestrogen Receptor ,-Immunoreactivity in Gonadotropin Releasing Hormone-Expressing Neurones: Regulation by Oestrogen

JOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2001
I. Kalló
Abstract Double-label immunohistochemistry was employed to establish whether immunoreactivity for the , subtype of the oestrogen receptor (ER,-IR) is present in gonadotropin releasing hormone (GnRH)-containing cells. In the immortalized GnRH cell line, GT1-7, almost all nuclei were immunoreactive for ER,. In the preoptic area of ovariectomized rats, more than one-half of the GnRH neurones (52.0,63.5%) contained ER,-IR within the nucleus; a smaller proportion of these neurones (5,10%) displayed a particularly intense nuclear signal for ER,. The presence of ER,-IR in the nuclei of GT1-7 cells and GnRH neurones is consistent with recent reports of ER, mRNA in these cells. Oestrogen treatment reduced the percentage of GnRH neurones with detectable ER,-IR. The range of signal intensity for ER, and the incidence of the ER, signal in GnRH neurones were comparable following double-label immunohistochemistry involving either bright field or fluorescent techniques. These findings raise the possibility that ER, receptors mediate direct effects of oestrogen on GnRH neurones. [source]

Effects of Chronic Oestrogen Replacement on Stress-Induced Activation of Hypothalamic-Pituitary-Adrenal Axis Control Pathways

JOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2000
C. V. Dayas
Abstract Oestrogen replacement therapy reportedly suppresses hypothalamic-pituitary-adrenal (HPA) axis responses to an emotional stressor in postmenopausal women. However, most studies in the rat suggest a facilitatory role for oestrogen in the control of HPA axis function. One explanation for this difference may be the regimen of oestrogen replacement: during oestrogen replacement therapy, oestrogen levels are low and constant whereas most animal studies examined the HPA axis response when oestrogen levels are rising. In the present study, we assessed HPA axis stress responses in mature ovariectomized rats after plasma oestrogen levels had been maintained at physiological levels for a prolonged period (25 or 100 pg/ml for 7 days). In the case of both an emotional stressor (noise) and a physical stressor (immune challenge by systemic interleukin-1, administration), oestrogen replacement suppressed stress-related Fos-like immunolabelling, in hypothalamic neuroendocrine cells and plasma adrenocorticotropin hormone responses. From the present data, and past reports, it appears unlikely that these effects of oestrogen are due to a direct action on corticotropin-releasing factor or oxytocin cells. Therefore, to obtain some indication of oestrogen's possible site(s) of action, Fos-like immunolabelling was mapped in the amygdala and in brainstem catecholamine groups, which are neuronal populations demonstrating substantial evidence of involvement in the generation of HPA axis stress responses. In the amygdala, oestrogen replacement suppressed central nucleus responses to immune challenge, but not to noise. Amongst catecholamine cells, oestrogen replacement was more effective against responses to noise than immune challenge, suppressing A1 and A2 (noradrenergic) and C2 (adrenergic) responses to noise, but only A1 responses to immune challenge. These data suggest that, as in postmenopausal women on oestrogen replacement therapy, chronic low-level oestrogen replacement can suppress HPA axis stress responses in the rat. Moreover, oestrogen appears to exert effects at multiple sites within putative HPA axis control pathways, even though most of the relevant neuronal populations do not contain genomic receptors for this gonadal steroid and the pattern of oestrogen action differs for an emotional vs a physical stressor. [source]

Regional and Selective Effects of Oestradiol and Progesterone on NMDA and AMPA Receptors in the Rat Brain

JOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2000

We investigated the effect of 10 months ovariectomy and a correction therapy, 2 weeks before the rats were killed, of oestradiol, progesterone or their combination on NMDA and AMPA receptor binding in the hippocampus, dentate gyrus, striatum, nucleus accumbens and frontal cortex of the rat brain as well as on amino acid levels in frontal cortex. NMDA and AMPA binding densities were assayed by autoradiography using, respectively, l -[3H]glutamate and [3H]AMPA; amino acid concentrations were measured by high performance liquid chromatograhy (HPLC) coupled with UV detection. Ovariectomy was without effect on NMDA and AMPA binding density in all brain regions assayed except in the hippocampal CA1 region and dentate gyrus where it decreased NMDA binding density compared to intact rats values. Oestradiol restored and increased NMDA binding density in the CA1 subfield and the dentate gyrus of ovariectomized rats but, by contrast, it decreased binding density in the striatum and in the frontal cortex while having no effect in the CA2/3 subfield of the hippocampus and in the nucleus accumbens. Oestradiol was without effect on AMPA binding density in the hippocampus and the dentate gyrus but it reduced AMPA binding density in the striatum, the frontal cortex and the nucleus accumbens. Progesterone, and oestradiol combined with progesterone, decreased NMDA but not AMPA binding density in the frontal cortex of ovariectomized rats, and they were without effect on these receptors in the other brain regions assayed. Amino acid concentrations in the frontal cortex were unchanged after ovariectomy or steroid treatments. The effect of oestradiol in the hippocampus confirmed in the present study and our novel findings in the frontal cortex, striatum and nucleus accumbens may have functional significance for schizophrenia and neurodegenerative diseases. [source]

Effects of vibration treatment on tibial bone of ovariectomized rats analyzed by in vivo micro-CT

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2010
Julienne E.M. Brouwers
Abstract Daily low-amplitude, high-frequency whole-body vibration (WBV) treatment can increase bone formation rates and bone volume in rodents. Its effects vary, however, with vibration characteristics and study design, and effects on 3D bone microstructure of ovariectomized animals over time have not been documented. Our goal was to determine the effects of WBV on tibial bone of ovariectomized, mature rats over time using an in vivo micro-CT scanner. Adult rats were divided into: ovariectomy (OVX) (n,=,8), SHAM-OVX (n,=,8), OVX and WBV treatment (n,=,7). Eight weeks after OVX, rats in the vibration group were placed on a vibrating platform for 20,min at 0.3,g and 90 Hertz. This was done 5 days a week for six weeks, twice a day. Zero, 8, 10, 12 and 14 weeks after OVX, in vivo micro-CT scans were made (vivaCT 40, Scanco Medical AG) of the proximal and diaphyseal tibia. After sacrifice, all tibiae were dissected and tested in three-point bending. In the metaphysis between 8 to 12 weeks after OVX, WBV treatment did not alter structural parameters compared to the OVX group and both groups continued to show deterioration of bone structure. In the epiphysis, structural parameters were not altered. WBV also did not affect cortical bone and its bending properties. To summarize, no substantial effects of 6 weeks of low-magnitude, high-frequency vibration treatment on tibial bone microstructure and strength in ovariectomized rats were found. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:62,69, 2010 [source]

Effects of h-PTH on cancellous bone mass, connectivity, and bone strength in ovariectomized rats with and without sciatic-neurectomy

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2004
Y. 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]

Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in rats

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2001
Ralph A. Meyer Jr.
The impact of age and ovariectomy on the healing of femoral fractures was studied in three groups of female rats at 8, 32 and 50 weeks of age at fracture. In the two older groups, the rats had been subjected to ovariectomy or sham surgery at random at 26 weeks of age. At fracture, all rats received unilateral intramedullary pinning of one femur and a middiaphyseal fracture. Rigidity and breaking load of the femora were evaluated at varying times up to 24 weeks after fracture induction by three-point bending to failure. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. In the youngest group, 8-week-old female rats regained normal femoral rigidity and breaking load by 4 weeks after fracture. They exceeded normal contralateral values by 8 weeks after fracture. In the middle group, at 32 weeks of age, fractures were induced, and the femora were harvested at 6 and 12 weeks after fracture. At 6 weeks after fracture there was partial restoration of rigidity and breaking load. At 12 weeks after fracture, only the sham-operated rats had regained normal biomechanical values in their fractured femora, while the fractured femora of the ovariectomized rats remained significantly lower in both rigidity and breaking load. In contrast, for the oldest group of rats, 50 weeks old at fracture, neither sham-operated nor ovariectomized rats regained normal rigidity or breaking load in their fractured femora within the 24 weeks in which they were studied. In all fractured bones, there was a significant increase in BMD over the contralateral intact femora due to the increased bone tissue and bone mineral in the fracture callus. Ovariectomy significantly reduced the BMD of the intact femora and also reduced the gain in BMD by the fractured femora. In conclusion, age and ovariectomy significantly impair the process of fracture healing in female rats as judged by measurements of rigidity and breaking load in three-point bending and by accretion of mineral into the fracture callus. © 2001 Orthopaedic Research Society. Published by Elsevier Science 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 rats

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008
Makoto 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]

D-003 does not possess oestrogenic potential in-vivo: findings of the uterotrophic assay

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2007
Miriam Noa
D-003 is a mixture of long-chain fatty acids purified from sugarcane wax that inhibits both cholesterol synthesis prior to mevalonate formation, and lipid peroxidation. D-003 has been shown to prevent bone loss and bone resorption in ovariectomized rats, and significantly improves bone resorption markers in postmenopausal women with reduced bone mineral density. As hormone-replacement therapy, D-003 displays cholesterol-lowering and anti-resorptive effects. We have studied its potential oestrogenic activity in-vivo using the uterotrophic assay. Rats were randomly distributed into five groups: a sham-operated group and four groups of ovariectomized rats, one treated with vehicle, one with D-003 (50 mg kg,1), one with oestradiol benzoate (30 ,g kg,1) and one with D-003 (50 mg kg,1) plus oestradiol benzoate (30 ,g kg,1). Treatments were administered for 14 days. Ovariectomy decreased the values of relative uterus weight, epithelium cell height and endometrial thickness compared with sham-operated rats, and these effects were all significantly reduced with oestradiol benzoate, but not with D-003. Concurrent administration of D-003 and oestradiol benzoate had statistically similar effects on all variables as oestradiol benzoate alone. In conclusions, D-003 orally given at 50 mg kg,1, a dose that prevents bone loss and bone resorption in ovariectomized rats, did not display oestrogenic/anti-oestrogenic activity in-vivo, as assessed in the uterotrophic assay. [source]

Alteration in G Proteins and Prolactin Levels in Pituitary After Ethanol and Estrogen Treatment

ALCOHOLISM, Issue 5 2008
Kirti Chaturvedi
Background:, Chronic administration of ethanol increases plasma prolactin levels and enhances estradiol's mitogenic action on the lactotropes of the pituitary gland. The present study was conducted to determine the changes in the pituitary levels of G proteins during the tumor development following alcohol and ethanol treatments. Methods:, Using ovariectomized Fischer-344 female rats, we have determined ethanol and estradiol actions at 2 and 4 weeks on pituitary weight and pituitary cell contents of prolactin, Gs. Gq11, Gi1, Gi2, and Gi3 proteins. Western blots were employed to measure protein contents. Results:, Ethanol increased basal and estradiol-enhanced wet weight and the prolactin content in the pituitary in a time-dependent manner. Chronic exposure of estradiol increased the levels of Gs protein in the pituitary. Unlike estradiol, ethanol exposure did not show significant effect on the basal level of Gs protein, but moderately increased the estradiol-induced levels of this protein. Estradiol exposure enhanced Gq11 protein levels in the pituitary after 2 and 4 weeks, while ethanol treatment failed to alter these protein levels in the pituitary in control-treated or estradiol-treated ovariectomized rats. In the case of Gi1, estradiol but not ethanol increased the level of this protein at 4 weeks of treatment. However, estradiol and ethanol alone reduced the levels of both Gi2 and Gi3 proteins at 2 and 4 weeks of treatment. Ethanol also significantly reduced the estradiol-induced Gi2 levels at 4 weeks and Gi3 level at 2 and 4 weeks. Conclusions:, These results confirm ethanol's and estradiol's growth-promoting and prolactin stimulating actions on lactotropes of the pituitary and further provide evidence that ethanol and estradiol may control lactotropic cell functions by altering expression of specific group of G proteins in the pituitary. [source]

Ethanol Alters Production and Secretion of Estrogen-Regulated Growth Factors That Control Prolactin-Secreting Tumors in the Pituitary

ALCOHOLISM, Issue 12 2007
Dipak K. Sarkar
Background:, Chronic administration of ethanol increases plasma prolactin levels and enhances estradiol's mitogenic action on the lactotropes of the pituitary gland. The present study was conducted to determine whether ethanol's lactotropic cell-proliferating action, like estradiol's, is associated with alteration in the production of 3 peptides that regulate cell growth: transforming growth factor beta 1 (TGF-,1), TGF-,3 and basic fibroblast growth factor (bFGF). Methods:, Using ovariectomized Fischer-344 female rats, we determined ethanol's and estradiol's actions on lactotropic cell proliferation and growth-regulatory peptide production and release in the pituitary gland during tumorigenesis. Results:, Ethanol increased basal and estradiol-enhanced mitosis of lactotropes in the pituitary glands of ovariectomized rats. The level of growth-inhibitory TGF-,1 was reduced in the pituitary following ethanol and/or estradiol treatment for 2 and 4 weeks. In contrast, ethanol and estradiol alone as well as together increased levels of growth-stimulatory TGF-,3 and bFGF in the pituitary at 2 and 4 weeks. In primary cultures of pituitary cells, both ethanol and estradiol reduced TGF-,1 release and increased TGF-,3 and bFGF release at 24 hours. Ethanol's effect on growth factor levels in the pituitary or growth factor release from the pituitary cells was less than that of estradiol. When ethanol and estradiol were applied together, their individual effects on these growth factors were amplified. Conclusions:, These results confirm estradiol's modulation of pituitary growth factor production and release, and provide evidence that ethanol, like estradiol, alters the production and secretion of growth-regulatory peptides controlling lactotropic cell proliferation. [source]

Cryopreservation of vascularized ovary: An evaluation of histology and function in rats

MICROSURGERY, Issue 5 2008
Shijie Qi M.D.
Cryopreservation of organs has been investigated to sustain the reproductive function of patients undergoing sterilizing chemotherapy and radiotherapy or reproductive surgery. A modified protocol for whole organ cryopreservation was described and the outcome of cryopreservative ovaries was evaluated, and apoptosis of cryopreservative cells stored for different time period and the viability of cryopreserved cells stored at different temperature was examined in rats. Lewis rat ovarian grafts were perfused for 30 min at 0.35 ml/min with M2 medium containing 0.1M fructose and increasing concentrations of 0,1.5M dimethylsulfoxide, cooled to ,140°C controlled by a computerized program, and stored in liquid nitrogen (,196°C) for 24 hours. After being thawed, ovaries were transplanted to syngeneic recipients after bilateral oophorectomy. Graft functions were monitored postoperatively. The major findings were that: 1) A 100% survival rate of rat ovaries was achieved in this study. Ovarian hormone secretion recovered in 80% rats which had received cryopreservative ovarian grafts. Postoperative serum estradiol levels in the cryopreservative graft group were lower than in the sham surgery control, but much higher than in the bilateral oophorectomy group. 2) Histological examination of cryopreservative ovarian grafts showed preantral and antral follicles. Two gestations were obtained. 3) Estradiol levels remained low in ovariectomized rats while in the oophorectomized rats given cryopreservative ovarian grafts levels started to rise after 14 ± 3 days. 4) The average viability in the cells from cryopreservative ovary organ (,196°C) was about 71 ± 18% compared to 90 ± 9% of fresh cells. This success should encourage further improvement of cryopreservative techniques for large organs. © 2008 Wiley-Liss, Inc. Microsurgery, 2008. [source]

Menatetrenone (Vitamin K2) and Bone Quality in the Treatment of Postmenopausal Osteoporosis

NUTRITION REVIEWS, Issue 12 2006
Jun Iwamoto MD
Menatetrenone (vitamin K2) reduces the incidence of vertebral fractures but has only modest effects on bone mineral density (BMD) in postmenopausal women with osteoporosis. Combined treatment with bisphosphonates and menatetrenone may be more effective than treatment with bisphosphonates alone in preventing vertebral fractures, despite the lack of an additive effect of menatetrenone on the BMD increase by bisphosphonates. Menatetrenone improves bone architecture in ovariectomized rats, and the mineral/ matrix ratio of the bone in terms of matrix volume and bone strength (without increasing bone mass) in rats with magnesium deficiency. Thus, available evidence supports an effect of menatetrenone on bone quality during osteoporosis treatment [source]

A hot water extract of Chlorella pyrenoidosa reduces body weight and serum lipids in ovariectomized rats

Post-translational Regulation of Endothelial Nitric Oxide Synthase (eNOS) by Estrogens in the Rat Vagina

THE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010
Biljana Musicki PhD
ABSTRACT Introduction., Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Aims., Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. Methods., We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17, (15 µg). Main Outcome Measures., Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. Results., We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. Conclusions., These results define novel estrogen signaling mechanisms in the vagina which involve eNOS phosphorylation and eNOS,caveolin-1 interaction. Musicki B, Liu T, Strong TD, Lagoda GA, Bivalacqua TJ, and Burnett AL. Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina. J Sex Med 2010;7:1768,1777. [source]

The Effect of Ovariectomy on Rat Vaginal Tissue Contractility and Histomorphology

THE JOURNAL OF SEXUAL MEDICINE, Issue 2 2006
F. Fatih Önol MD
ABSTRACT Introduction., Ovarian hormones have an important role in age-related genital arousal disorders; however, our knowledge regarding possible vaginal wall morphology and contractility changes in low-hormonal states is limited. Aims., To investigate morphological and functional alterations in the vaginal tissue in a rat ovariectomy model and to show the differences between proximal and distal vagina. Methods., Six weeks following ovariectomy, vaginal tissues were examined under light and electron microscopy. Circularly cut distal and proximal tissues were studied in the organ bath under isometric tension and compared with age-matched controls. Contractile responses to electrical field stimulation (EFS), phenylephrine, carbachol, and the effects of alpha-1 and alpha-2 blockade on EFS-induced contractility were investigated. Relaxation responses to EFS and vardenafil were investigated in precontracted strips. Main Outcome Measures., Differences between control and ovariectomy groups in terms of vaginal tissue contractility and histomorphological properties. Results., Distal vagina showed different epithelial characteristics and a better-developed muscularis compared with proximal vagina. Ovariectomy caused thinning of the epithelium, severe degeneration in epithelial architecture, and smooth muscle atrophy. Contraction and relaxation responses of distal strips were significantly lower in ovariectomized rats. Contractile responses to neuropharmacological stimulation were insignificant in proximal strips of both groups. EFS-induced contractions in distal strips diminished significantly after alpha-1 and alpha-2 adrenergic blockade. EFS caused frequency-dependent relaxation responses in precontracted distal strips, which were significantly decreased after nitric oxide synthase inhibition. Conclusions., Ovariectomy causes significant alteration in rat vaginal tissue morphology and contractility. Contraction and relaxation responses of distal vagina are significantly greater compared with morphologically distinct proximal vagina. Alpha-1 and alpha-2 receptors are the main mediators of contraction in distal rat vaginal tissue whereas nitric oxide pathway may have at least a partial role in relaxation. Main mediators of the rat vaginal tissue relaxation and the effect of ovariectomy on this regulation are yet to be defined. Önol FF, Ercan F, and Tarcan T. The effect of ovariectomy on rat vaginal tissue contractility and histomorphology. J Sex Med 2006;3:233,241. [source]

Oestrogen Promotes Coronary Angiogenesis even under Normoxic Conditions

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2008
Mehdi Nematbakhsh
Oestrogen has angiogenic properties under hypoxic condition, and if oestrogen also induces angiogenesis under normoxic condition, it could be used in combination with other angiogenic therapies in the treatment of ischaemic heart disease. In this study, we evaluated the angiogenic effect of high-dose oestrogen treatment in normoxic rat heart tissue. Fifty-two ovariectomized rats were randomized in oestrogen-treated and control groups. 17,-Oestradiol (1 mg/week) and normal saline (1 mg/week) were administered intramuscularly in the treatment and control groups for 2 months. After that, coronary capillary density and coronary vessel permeability were measured. The serum vascular endothelial growth factor (VEGF) level was also measured before and after the treatment. The results indicate that coronary capillary density (number of capillary per square millimetre) and coronary vessel permeability (fluorescence intensity) were significantly higher in the oestrogen-treated group than in the control group (628 ± 26 per mm2 versus 540 ± 26 per mm2; P < 0.05 and 207 ± 10 versus 147 ± 19 per gram tissue; P < 0.05). Oestrogen treatment increased serum VEGF level in the oestrogen-treated group compared to the control group (52 ± 3 versus 33 ± 6 pg/ml; P < 0.05), but interestingly VEGF was also increased in the control group after placebo treatment. It seems that high-dose oestrogen administration has angiogenic properties even in normoxic conditions. These angiogenic properties may result from oestrogen's direct effect on VEGF or other mechanisms, such as endothelial progenitor cell mobilization. Because of the broad effect of oestrogen on angiogenic growth factors and endothelial cells, more studies are required to clarify angiogenic properties of high-dose oestrogen. [source]

A combination of soy isoflavone supplementation and exercise improves lipid profiles and protects antioxidant defense-systems against exercise-induced oxidative stress in ovariectomized rats

BIOFACTORS, Issue 4 2007
Hea Young Oh
Abstract Menopause is often accompanied with weight gain, metabolic lipid abnormalities, and oxidative stress. In this study, we investigated the combined effects of exercise and soy isoflavone supplemention on the lipid profiles and antioxidant capacities of ovariectomized rats. Twenty-five female Sprague-Dawley rats were divided into 5 groups: sham-operated, ovariectomized (OVX), OVX with exercise (OVX + EX), OVX with soy isoflavone supplementation (OVX + ISO), and OVX with both soy isoflavones and exercise (OVX + ISO + EX). After 12 weeks of intervention, antioxidant status was evaluated in collected blood samples by the ferric reducing ability of plasma (FRAP), glutathione (GSH) content, and sodium oxide dismutase (SOD) activity. DNA damage in the lymphocytes was determined using alkaline single-cell gel electrophoresis (the Comet assay). Although there were no significant differences in weight gain and food intake, weight gain was lower in OVX + EX, OVX + ISO, and OVX + ISO + EX than in OVX. OVX + EX, OVX + ISO, and OVX + ISO + EX showed a significant decrease in total cholesterol, triglycerides, and LDL-cholesterol compared to OVX. The soy isoflavone supplemented group had significantly increased FRAP values and GSH contents in contrast to no changes in the exercised group, whereas exercise markedly increased SOD activity and H2O2 -induced DNA tail length and tail moment. Exercise with soy isoflavone supplementation significantly increased FRAP values and had no difference on SOD activity, including DNA damage. These results demonstrate that a combined treatment of moderate exercise and soy isoflavone supplementation could exert a beneficial effect on weight control and lipid profiles, and offer protection from exercise-induced oxidative stress in postmenopausal women. [source]