Estrogen Replacement Group Research Articles

Oral Administration of Artemisia argyi Polysaccharide Increases Estrogen Level and Maintains Blood Lipid Homeostasis in Ovariectomized Rats

Introduction: Artemisia argyi polysaccharide (AAP) has a beneficial effect on menstruation-related symptoms and the potential regulation of lipid metabolism. It is expected to be a safe and effective ingredient for estrogen deficiency and lipid metabolic disorders. Here, we investigate the effect of AAP on body weight gain, estrogen level, and blood lipid changes in ovariectomized (OVX) rats. Methods: Thirty-six female Wistar rats were randomly divided into six treatment groups, including a sham-operated (Sham) group, OVX group, estrogen replacement (OVX + E2) group, and AAP treatment (OVX + 125, 250, 500 mg/kg AAP) group. The body weight and feed intake were recorded every week. The level of estrogen and blood lipid was determined. The gene expressions and protein expressions of estrogen receptors (ERs), fatty acid synthetase (FAS), acetyl CoA carboxylase 2 (ACC2), and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) were determined. Results: AAP treatment significantly decreased the body weight gain and average daily food intake of rats in the OVX group. Treatment with AAP significantly increased the relative weight of the uterus, plasma estrogen level, and the gene expression and protein expression of ER-α in the uterus. For blood lipids, plasma levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced by AAP treatment in OVX rats. AAP treatment decreased the expression of FAS and HMGR in the liver of OVX rats. Furthermore, AAP treatment significantly increased the gene expression of ACC2, the protein expression of P-ACC2, and the ratio of P-ACC2/ACC2. Conclusion: In summary, AAP treatment exerts beneficial effects on body weight gain and lipid metabolism disorder induced by ovariectomy through increasing estrogen levels, inhibiting FAS, and promoting fatty acid oxidation.

Estrogen Replacement Reduces Hearing Threshold Shifts and Cochlear Hair Cell Loss After Acoustic Overexposure in Ovariectomized Rats.

Objectives.The relationship of estrogen (the primary female sex hormone) with hearing function has been studied in both humans and animals. However, whether estrogen levels affect hearing remains uncertain. Therefore, in this study, we investigated changes in the vulnerability of hearing to acoustic overexposure in ovariectomized female rats.Methods.Eighteen 8-week-old female Sprague-Dawley rats were separated into four groups as follows: sham ovariectomy (OP), OP only, and OP treated with low (10 µg/kg) or high doses (100 µg/kg) of estrogen. Rats in the estrogen replacement groups were given two intraperitoneal injections. Hearing thresholds were measured before noise exposure, and at 1 day and 2 weeks after exposure.Results.The hearing thresholds of the sham OP and OP-only groups were not significantly different. However, both estrogen groups showed a lower threshold shift than the OP-only group. Histological immunostaining analyses showed that hair cell loss in the 32 kHz region was more severe in the sham OP group than in the OP-only group. Furthermore, there was little or no hair cell loss in either estrogen replacement group and significantly more hair cell loss in the OP-only group.Conclusion.These results suggest that estrogen replacement may reduce the vulnerability of hearing to noise exposure in menopausal women.

Impact of Adrenal Hormone Supplementation on Bone Geometry in Growing Teens With Anorexia Nervosa

PurposeAdolescents with anorexia nervosa (AN) have decreased dehydroepiandrosterone (DHEA) and estrogen concentrations that may contribute to skeletal deficits. We sought to determine whether DHEA + estrogen replacement (ERT) prevented bone loss in young adolescents with AN. MethodsWe recruited females with AN (n = 70, ages 11–18 years) into a 12-month, randomized, double-blind placebo-controlled trial. Participants were randomized to oral micronized DHEA 50 mg + 20 mcg ethinyl estradiol/.1 mg levonorgestrel daily (n = 35) or placebo (n = 35). Outcomes included serial measures of bone mineral density (BMD) by dual-energy X-ray absorptiometry (total body, hip, spine) and peripheral quantitative computed tomography (pQCT; tibia). Magnetic resonance imaging of T1-weighted images of the left knee determined physeal status (open/closed). ResultsSixty-two subjects completed the trial. Physeal closure status was the strongest predictor of aBMD changes. Among girls with open physes, those who received DHEA + ERT showed a decline in BMD Z-scores compared with those receiving placebo, whereas there was no effect in those with at least one closed physis. Treatment did not affect any pQCT measures, regardless of physeal closure status. ConclusionsCombined DHEA + ERT did not significantly improve dual-energy X-ray absorptiometry or pQCT BMD measurements in young adolescent girls with AN, in contrast to an earlier trial showing benefit in older adolescents and young women. In girls with open physes, the mean change in the placebo arm was greater than that of the DHEA + ERT group. We conclude that DHEA + ERT is ineffective for preserving bone health in growing young adolescents with AN at the dose and route of administration described in this report.

Effects of Resveratrol on the Mechanisms of Antioxidants and Estrogen in Alzheimer's Disease.

Objective To observe the effects of resveratrol (Res) on the antioxidative function and estrogen level in an Alzheimer's disease (AD) mouse model. Methods First, we examined the effects of Res on an AD mice model. SAMP8 mice were selected as the model, and normal-aging SAMR1 mice were used as the control group. The model mice were randomly divided into three groups: a model group, high-dose Res group (40mg/kg, intraperitoneal (ip)), and low-dose Res group (20mg/kg, ip). After receiving medication for 15 days, the mice were subjected to the water maze test to assess their spatial discrimination. The spectrophotometric method was used to detect the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) as well as the malondialdehyde (MDA) content. Quantitative PCR (q-PCR) was used to detect SOD, GSH-Px, CAT, and heme oxygenase-1 (HO-1) mRNA level changes. Western blot analysis detected HO-1 and Nrf2 protein expression. Second, we researched the effect of Res on the estrogen level in the SAMP8 model mice. The model mice were randomly divided into four groups: a model group, estrogen replacement group (0.28 mg/kg, intramuscular (im), estradiol benzoate), high-dose Res group (5 mg/kg, im), and low-dose Res group (2.5 mg/kg, im). The mice were injected, once every three days, for 5 weeks. Q-PCR was used to detect brain tissue mRNA expression changes. Western blot analysis detected ERα, ERβ, and ChAT protein expression. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the expression of E2 and amyloid β protein (Aβ) in brain tissue. Results Compared with the control treatment, Res could improve the spatial abilities of the mice to a certain extent and also increase the expression of SOD, GSH-Px, CAT, and HO-1 at the mRNA level (P<0.05). In addition, enhanced SOD, GSH-Px, and CAT activities and HO-1 protein levels and decreased MDA content (P<0.05) were detected in the brain tissue of the Res-treated mice. The cytoplasmic Nrf2 content in the Res-treated mice was also decreased while the nuclear Nrf2 content and the nuclear translation rate of Nrf2 were increased (P<0.05). Res could decrease the expression of ERβ in the brain tissue at the mRNA and protein levels and the expression of Aβ in the brain tissue at the protein level. Res could also increase the mRNA and protein expression of ERα and ChAT and the protein expression of estradiol in the brain tissue. Conclusion Res can increase the antioxidant capacity of AD models through the Nrf2/HO-1 signaling pathway. In addition, Res can enhance estrogen levels in an AD model. These findings provide a new idea for the treatment of AD.

Effects of estrogen replacement therapy on the myelin sheath ultrastructure of myelinated fibers in the white matter of middle-aged ovariectomized rats.

The effects of estrogen replacement therapy (ORT) on white matter and the myelin sheath ultrastructure in the white matter of middle-aged ovariectomized (OVX) rats were investigated in this study. Middle-aged rats were ovariectomized and divided into a placebo replacement (OVX + O) group and an estrogen replacement (OVX + E) group. Then, the Morris water maze, electron microscope techniques, and stereological methods were used to investigate the effects of ORT on spatial learning capacity, white matter volume and the myelin sheath ultrastructure in the white matter. We found that the spatial learning capacity of the OVX + E rats was significantly improved compared with that of the OVX + O rats. When compared with that of OVX + O rats, the total volume of the myelin sheaths in the white matter of the OVX + E rats was significantly increased by 27%, and the difference between the outer perimeter and inner perimeter of the myelin sheaths of the white matter in the OVX + E rats increased significantly by 12.6%. The myelinated fibers with mean diameters of 1.2-1.4 μm were significantly longer (46.1%) in the OVX + E rats; the difference between the mean diameter of myelinated fibers and the mean diameter of axons (0-0.4 μm) was significantly increased by 21.6% in the OVX + E rats. These results suggested that ORT had positive protective effects on the spatial learning ability and on the myelin sheath ultrastructure in the white matter of middle-aged OVX rats.

Effects of Estrogen on Insulin Sensitivity and Adipokines in Mice.

To study the potential mechanisms via which estrogen exerts its effects on the insulin sensitivity in mice. Totally 36 female C57BL/6J mice aged 6 weeks were randomly divided into six groups:normal diet (NOR) group, normal diet with ovariectomy (NOR+OVX) group, normal diet with ovariectomy and estrogen replacement (NOR+OVX+E2) group,high-fat diet (HF) group, high-fat diet with ovariectomy (HF+OVX) group, and high-fat diet with ovariectomy and estrogen replacement (HF+OVX+E2) group. There were six mice in each group. After the ovariectomy based on the grouping, the mice were given normal diet or high-fat diet for 20 weeks. The intervention groups were given estrogen (5 μg/d,subcutaneous injection) for 20 days. Then,the body weight,visceral fat weight,oral glucose tolerance and insulin sensitivity (by euglycemic hyperinsulinemic clamp test), and serum leptin, adiponectin,and resistin levels were compared among these six groups. Compared with HF group, the HF+OVX group had significantly higher body weight and visceral fat weight and lower glucose tolerance, which were significantly improved after estrogen replacement therapy (all P<0.05). However, these indicators showed no significant differences among groups with normal diets (all P>0.05). The insulin sensitivity of ovariectomized mice was significantly decreased in both high-fat and normal diet groups and was also improved significantly after estrogen replacement (P<0.05). The serum leptin was increased and adiponectin was decreased significantly in ovariectomized mice, and the improvements of these two adipokines were also statistically significant after estrogen therapy (P<0.05): however,the serum resistin level was not significantly different among these 6 groups (P>0.05). Estrogen replacement therapy can improve insulin resistance by lowering body weight. In addition, it can exert its effect directly on adipose tissue,improve the levels of adipokines,reduce the amount of visceral fat, and improve insulin sensitivity in mice.

Delay in post-ovariectomy estrogen replacement negates estrogen-induced augmentation of post-exercise muscle satellite cell proliferation

This study examined the effects of a delay in post-ovariectomy replacement of 17β-estradiol (estrogen) on the post-exercise proliferation of muscle satellite cells. Nine-week-old, ovariectomized, female Sprague-Dawley rats (n = 64) were distributed among 8 groups based on estrogen status (0.25 mg estrogen pellet or sham), exercise status (90 min run at 17 m·min(-1) and a grade of -13.5° or unexercised), and estrogen replacement ("proximal", estrogen replacement within 2 weeks; or "delayed", estrogen replacement at 11 weeks following ovariectomy). Significant increases in satellite cells were found in the soleus and white gastrocnemius muscle (immunofluorescent colocalization of nuclei with Pax7) 72 h following eccentric exercise (p < 0.05) in all exercised groups. Proximal E2 replacement resulted in a further augmentation of muscle satellite cells in exercised rats (p < 0.05) relative to the delayed estrogen replacement group. Expression of PI3K was unaltered and phosphorylation of Akt relative to total Akt increased following estrogen supplementation and exercise. Exercise alone did not alter the expression levels of Akt. An 11 week delay in post-ovariectomy estrogen replacement negated the augmenting influence seen with proximal (2 week delay) post-ovariectomy estrogen replacement on post-exercise muscle satellite cell proliferation. This effect appears to be independent of the PI3K-Akt signaling pathway.

Estrogen replacement improves skeletal muscle performance by increasing parvalbumin levels in ovariectomized rats

Muscle weakness is common during menopause. Effective estrogen replacement was hypothesized to prevent sarcopenia. This study aimed to investigate the estrogen level, estrogen receptors (α and β) immunoreactivities, muscle mass and functions, and parvalbumin (PV) levels in the extensor digitorum longus (EDL) and the gastrocnemius muscles of ovariectomized rats. Adult female Wistar rats (12 weeks old) were divided into five groups: sham-operated (SHAM), and ovariectomized (E0) groups that received 10 weeks of estrogen replacements of 0μg/kg (E0), 10μg/kg (E10), 20μg/kg (E20) and 40μg/kg (E40). The estrogen levels, ER α and ER β immunoreactivities, muscle fiber sizes and contractivities and the PV levels were reduced in the E0 group, but increased in all the estrogen replacement groups in both muscles. This study indicated that the reduction of estrogen levels led to a decrease of both ER α and ER β resulting in a decline in muscle mass and PV levels. The decrease of PV levels affected muscle performance, whereas estrogen replacement increased both the ER α and ER β. The increase in the PV levels may result in an improvement of muscle performance. This may explain one mechanism of estrogen on muscle mass and strength in estrogen dependent sarcopenia.

535 ESTROGEN CONTROLS BLADDER CONTRACTILE POWER THROUGH MYOSIN HEAVY CHAIN ISOFORMS

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology (II)1 Apr 2013535 ESTROGEN CONTROLS BLADDER CONTRACTILE POWER THROUGH MYOSIN HEAVY CHAIN ISOFORMS Ken Aikawa, Kei Ishibashi, Masanori Nomiya, Nobuhiro Kushida, Nobuhiro Haga, Norio Takahashi, Soichiro Ogawa, Yohei Kawashima, Yoshiyuki Kojima, and Osamu Yamaguchi Ken AikawaKen Aikawa Fukushima, Japan More articles by this author , Kei IshibashiKei Ishibashi Fukushima, Japan More articles by this author , Masanori NomiyaMasanori Nomiya Fukushima, Japan More articles by this author , Nobuhiro KushidaNobuhiro Kushida Fukushima, Japan More articles by this author , Nobuhiro HagaNobuhiro Haga Fukushima, Japan More articles by this author , Norio TakahashiNorio Takahashi Fukushima, Japan More articles by this author , Soichiro OgawaSoichiro Ogawa Fukushima, Japan More articles by this author , Yohei KawashimaYohei Kawashima Fukushima, Japan More articles by this author , Yoshiyuki KojimaYoshiyuki Kojima Fukushima, Japan More articles by this author , and Osamu YamaguchiOsamu Yamaguchi Koriyama, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1930AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urodynamic studies have shown that detrusor underactivity (DU) in women increases with age. One cause of this impaired bladder function that has recently attracted attention is estrogen deficiency. However, mechanisms underlying the association between estrogen deficiency and DU are still not understood. On the other hand, it is known that estrogen modulates the expression of myosin heavy chain (MHC) isoforms in smooth muscle. Thus, using a rat animal model, we investigated the effect of estrogen withdrawal and replacement on the expression of MHC isoforms and contractile power in bladder. METHODS Thirty female SD rats were divided into sham (Sham), bilateral ovariectomy (OVX), and OVX plus estrogen replacement (OVX+E) groups. The OVX+E group was given estradiol subcutaneously at 5 μg/kg/day for 4 weeks. At 4 weeks after surgery, each bladder was used for analysis of histology, MHC isoform (SM1, SM2) mRNA expression, and contractile power. Using bladder strips, the shortening responses to electrical field stimulation under various loads (4.9 mN to 19.6 mN) were recorded. The applied load was regarded as force generated (F), and velocity of shortening (V) was calculated from the shortening curve. Contractile power was defined as the total mechanical power (P), which is given by the following Hill equation: P = FV + aV + bF, where a and b are constants of each bladder strip. RESULTS Bladder weight and histological findings were not different between groups. The force/velocity plots obtained from the isotonic contraction study were well fitted to the Hill equation. Thus, contractile power for each strip could be determined. The contractile power significantly decreased in OVX, and estrogen replacement suppressed this decrease (Fig. 1a). The SM2/SM1 ratio significantly increased in OVX, and estrogen replacement suppressed this increase (Fig. 1b). CONCLUSIONS Our results suggest that estrogen maintains bladder contractile power via modulation of the expression of MHC isoforms. Clinical application of estrogen replacement may be beneficial for treating postmenopausal DU. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e220 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ken Aikawa Fukushima, Japan More articles by this author Kei Ishibashi Fukushima, Japan More articles by this author Masanori Nomiya Fukushima, Japan More articles by this author Nobuhiro Kushida Fukushima, Japan More articles by this author Nobuhiro Haga Fukushima, Japan More articles by this author Norio Takahashi Fukushima, Japan More articles by this author Soichiro Ogawa Fukushima, Japan More articles by this author Yohei Kawashima Fukushima, Japan More articles by this author Yoshiyuki Kojima Fukushima, Japan More articles by this author Osamu Yamaguchi Koriyama, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The Role of Estrogen on Rat Parotid Gland after Menopause

Objective: To determine the histopathological changes of estrogen deficiency and estrogen replacement treatment in parotid gland of ovariectomized rats. Method: Female albino rats were divided into 3 groups: sham, ovariectomized, and ovariectomized with estrogen replacement. Histopathological evaluation of rat parotid glands were done by using the diameter of acinus and striated duct (SD), height of SD, and interacinar connective tissue thickness. Apoptosis in parotid gland were examined by TUNEL staining. Results: Except interacinar connective tissue thickness, there were no significant differences between the sham-operated control and ovariectomized group in terms of the diameter of acinus and striated duct (SD) and height of SD. Estrogen replacement resulted in significant increase in the height of SD and interacinar connective tissue thickness. Apoptotic index was higher in both ovariectomized and estrogen replacement group compared to sham-operated control. Conclusion: Although estrogen replacement did not reduce apoptotic index in parotid gland of overiectomized rat, it may have some positive influence on saliva secretion by increasing interaciner connective tissue thickness.

Effects of Ovariectomy and Estrogen Replacement Therapy on Laryngeal Tissue

To determine the histopathological effect of estrogen deficiency and hormone replacement treatment on laryngeal tissue in ovariectomized rats. Animal study. The study was conducted at the animal experiment laboratory of Marmara University School of Medicine, Istanbul, Turkey. Six-month-old female Wistar albino rats were divided into the following 3 groups (n = 8 per group): sham-operated control, ovariectomized, and ovariectomized with estrogen replacement. Rats in the ovariectomized with estrogen replacement group received 17 β-estradiol valerate (200 µg/kg, subcutaneously) once a week. Animals were killed after 8 weeks of intervention. Significant changes were observed in the ovariectomized group when edema in lamina propria, inflammation in squamous, respiratory epithelia and lamina propria, pseudostratification, and cilia loss were assessed. Except cilia loss, there were no significant differences in the assessments between the sham-operated control and ovariectomized with estrogen replacement groups. On the basis of histopathological evaluations, it was shown that estrogen replacement helped to improve laryngeal changes due to experimentally induced menopause.

Labisia pumila extract down-regulates hydroxysteroid (11-beta) dehydrogenase 1 expression and corticosterone levels in ovariectomized rats

We evaluated the effects of a standardized Labisia pumila var. alata (LPva) extract on body weight change, hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) expressions and corticosterone (CORT) level in ovariectomized (OVX) rats. The decoction of LPva has been used for generations among Malay women in Malaysia to maintain a healthy reproductive system.Thirty-six Sprague-Dawley OVX rats were treated orally with LPva extract (10, 20 or 50 mg/kg/day) or estrogen replacement (ERT) for 30 days. Sham operated rats were used as controls. Compared to untreated OVX rats, LPva-treated rats showed less weight gain and had significantly down-regulated HSD11B1 mRNA in liver tissues. HSD11B1 mRNA in adipose tissues increased by 55% (p < 0.05) in OVX rats but normalized in rats treated with LPva. Similarly, there was significant down-regulation (p < 0.05) of protein levels of HSD11B1 in both liver and adipose tissue of LPva and ERT groups, and CORT levels were significantly reduced in both groups of rats. This is the first study ever conducted to evaluate the beneficial effects of LPva in relation to weight gain caused by estrogen insufficiency. Results implied that the bioactive components in LPva extract affect not only HSD11B1 expressions in both adipose and liver tissues but also decrease circulating CORT. The extract should be explored for its potential use as a natural remedy for weight management.

Effect of estrogen replacement on the histologic response to polypropylene mesh implanted in the rabbit vagina model

The aim of this study was to determine the effect of estrogen replacement after ovariectomy on the histologic response to polypropylene mesh implanted in rabbit vagina. Thirty rabbits were assigned to 5 groups: sham laparotomy, ovariectomy, ovariectomy-preoperative estrogen, ovariectomy-postoperative estrogen, or ovariectomy-preoperative and postoperative estrogen. Rabbits underwent sham surgery or ovariectomy and were infused with vehicle or 17beta-estradiol (200 microg/d) for 4 weeks ("preoperative" estrogen). Polypropylene mesh was implanted in the posterior vaginal wall, and rabbits were infused with vehicle or "postoperative" estrogen for an additional 8 weeks. Grafts were harvested and underwent histologic evaluation. Vaginal atrophy in ovariectomized rabbits was reversed by estrogen replacement. Scores for inflammation (P = .33) and neovascularization (P = .23) at the graft site were not different among estrogen replacement groups, but estrogen administration was associated with increased collagen deposition (P = .005). Estrogen replacement administered for 8 weeks postoperatively increases collagen deposition into polypropylene mesh.

Additional Weight Bearing during Exercise and Estrogen in the Rat: The Effect on Bone Mass, Turnover, and Structure

Mechanical loading and estrogen play important roles in bone homeostasis. The aim of this study was to evaluate the effects of mechanical loading on trabecular bone in the proximal femur of ovariectomized rats. We hypothesized that mechanical loading suppresses bone resorption and increases bone formation, which differs from the suppressive effects of estrogen on both resorption and formation. Furthermore, we expected to find changes in trabecular architecture elicited by the effects of mechanical loading and estrogen deficiency. Sixty female Wistar rats, 12 weeks old, were assigned to either the sedentary groups sham surgery (SED), ovariectomy (SED+OVX), and ovariectomy with estrogen replacement (SED+OVX+E2) or to the exercise groups EX, EX+OVX, EX+OVX+E2. Following ovariectomy, 5 microg 17beta-estradiol was given once weekly to the estrogen replacement groups. Exercise consisted of running with a backpack (load +/-20% of body weight) for 15 minutes/day, 5 days/week, for 19 weeks. Dual-energy X-ray absorptiometry (DXA) scans were performed before (T0), during (T6), and after (T19) the exercise period to obtain bone mineral content (BMC) and bone mineral density (BMD) data. After the exercise program, all rats were killed and right and left femora were dissected and prepared for micro-CT scanning and histomorphometric analysis of the proximal femoral metaphysis. After 19 weeks, increases in BMC (P = 0.010) and BMD (P = 0.031) were significant. At T19, mechanical loading had a significant effect on BMC (P = 0.025) and BMD (P = 0.010), and an interaction between mechanical loading and estrogen (P = 0.023) was observed. Bone volume and trabecular number decreased significantly after ovariectomy, while trabecular separation, mineralizing surface, bone formation rate, osteoclast surface, degree of anisotropy, and structure model index increased significantly after ovariectomy (P < 0.05). Trabecular bone turnover and structural parameters in the proximal femur were not affected by exercise. Estrogen deficiency resulted in a less dense and more oriented trabecular bone structure with increased marrow cavity and a decreased number of trabeculae. In conclusion, mechanical loading has beneficial effects on BMC and BMD of the ovariectomized rat. This indicates that the load in the backpack was high enough to elicit an osteogenic response sufficient to compensate for the ovariectomy-induced bone loss. The results confirm that estrogen suppresses both bone resorption and bone formation in the proximal metaphysis in the femoral head of our rat-with-backpack model. The effects of mechanical loading on the trabecular bone of the femoral head were not significant. This study suggests that the effect of mechanical loading in the rat-with-backpack model mainly occurs at cortical bone sites.

The effect of ovariectomy and long-term estrogen replacement on bladder structure and function in the rat.

PURPOSE The use of estrogen replacement therapy for treating postmenopausal urinary incontinence is a controversial topic. We examined the behavioral, cystometric and histological changes that occur with long-term estrogen depletion and supplementation in rat bladders to determine the role of menopause in lower urinary tract dysfunction. MATERIALS AND METHODS A total of 40 female Sprague-Dawley rats were placed into 1 of 3 groups, including bilateral ovariectomy, bilateral ovariectomy plus estrogen replacement and control. The estrogen replaced group received a 0.25 mg. 16-week sustained release pellet (Innovative Research of America, Sanasota, Florida) placed subcutaneously. After surgery voiding frequency and volume were measured in 24-hour periods by placing animals in metabolic cages. After 16 weeks the rats underwent catheterization and continuous cystometry. The bladder was then removed and stained with Gomori trichrome. The collagen-to-smooth muscle density ratio was calculated for each specimen using current imaging software. RESULTS There was no significant difference in voiding patterns in the 3 groups, as measured by volume and voiding frequency. Cystometric data showed a trend toward higher voiding pressure, threshold pressure, baseline pressure and mean inter-voiding pressure in the ovariectomy group compared with the estrogen and control groups, although there was no statistical significance. Histological studies showed a higher mean collagen-to-smooth muscle ratio plus or minus standard deviation in the ovariectomy group (0.807 +/- 0.204) than in the ovariectomy plus estrogen replacement (0.709 +/- 0.118) and control (0.700 +/- 0.129) groups (p <0.05). Furthermore, when histological and cystometric data were compared for individual samples, we found a direct correlation of mean inter-voiding pressure (a measure of bladder instability) with the collagen-to-smooth muscle ratio (p <0.05). CONCLUSIONS Long-term estrogen replacement is beneficial for treating postmenopausal urinary incontinence.

Chronic treatment with 17β-estradiol increases susceptibility of smooth muscle cells to nitric oxide

The purpose of this study was to evaluate the role of estrogen as a vasodilator or relaxing modulator during vascular tonus through chronic estrogen treatment. Experiments were conducted using isolated basilar arteries from ovariectomized female rabbits divided into two groups (the with and without estrogen replacement groups, respectively). Both acetylcholine and carbachol relaxed the basilar arteries of rabbits in the with estrogen replacement group (pre-contracted by 30 mM K+) more strongly than in the without estrogen replacement group. Vasodilatation effects of (±)-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3 -hexenamide (NOR1) and S-nitroso-N-acetyl-penicillamine (SNAP) were greater in rabbits in the with estrogen replacement group than the without estrogen replacement both with endothelium-intact and denuded preparations. On the other hand, vasodilatation effects of nicardipine, 17β-estradiol and membrane-permeable cyclic-GMP or cyclic-AMP were the same in both groups. These results suggest that chronic administration of estradiol potentiates reactivity to nitric oxide (NO) in smooth muscle cells, which could be a therapeutic target for cardiovascular diseases in postmenopausal women.

Effects of long-term estrogen replacement on social investigation and social memory in ovariectomized C57BL/6 mice

Estrogen has been shown to play a role in modulating social recognition memory. However, the literature regarding the influence of estrogen on social memory is sparse and only covers two experimental manipulations: acute injections and receptor knockout. Long-term effects of estrogen replacement on social investigation and social recognition are unknown. Furthermore, existing social recognition protocols focus on memory of very short durations (<2 h). In the present study, we examined long-term effects of estrogen replacement on both short- (<30 min) and long-term (24 h) social recognition in ovariectomized female C57BL/6 mice by implanting 60-day time-release pellets containing physiological doses of estradiol (0, 0.18, or 0.72 mg of 17β-estradiol). After 55 days of treatment, evidence of social recognition memory, measured by 24-h habituation, was found only in mice receiving the 0.72-mg pellet. This result is remarkable as previous reports indicate that individually-housed untreated rats and mice do not show habituation beyond 2 h. Our study further revealed that estrogen also increased frequencies of baseline social investigation without affecting general activity levels and decreased delayed post-swim-stress serum corticosterone concentration. Thus, these results suggest that long-term estrogen replacement increased the interest in social interaction as well as decreased stress responses. It is likely that the 24-h habituation observed in the estrogen replacement group is mediated jointly by the non-mnemonic effects of estrogen on the behavior displayed during the stage of memory encoding as well as mnemonic effects during the stage of memory consolidation.

Estrogen replacement and exercise capacity in postmenopausal women: A randomized placebo-controlled study

Objective. We tested the hypothesis that estrogen replacement (2 mg estradiol/day, orally for 90 days) would improve cardiopulmonary and functional capacities in postmenopausal women.Study design. Twenty-three postmenopausal and sedentary women were divided into estrogen replacement (n = 13, 57 ± 2 years) and placebo control (n = 10, 58 ± 2 years) groups. They performed a cardiopulmonary exercise test before and after the intervention.Results. Baseline measurements were similar between groups. Blood pressure and heart rate at rest and during exercise were unchanged by estrogen treatment, and estrogen did not alter pulmonary measurements at rest and during exercise. Oxygen consumption at anaerobic threshold, respiratory compensation point and peak exercise were lower after estrogen replacement, despite the unchanged workload and exercise time to exhaustion. In the placebo control group, no change in peak oxygen consumption, workload and time to exhaustion was found.Conclusions. Estrogen does not change cardiopulmonary responses to submaximal and maximal exercise in postmenopausal women. In addition, estrogen fails to improve exercise capacity in postmenopausal women.

Estrogen replacement therapy reverses changes in intramural coronary resistance arteries caused by female sex hormone depletion.

We tested the hypothesis that female sex hormone depletion and estradiol replacement therapy significantly influences the biomechanical properties of intramural coronary resistance arteries. Female rats (n=30) were divided into three groups. In group O, rats were subjected to bilateral ovariectomy. Group HRT was subjected to bilateral ovariectomy and estradiol replacement therapy. Rats in group C served as controls. One month after ovariectomy, intramural coronary arteries (approximately 200 microm in diameter) branching from the left anterior descending coronary were isolated, cannulated and studied by microarteriography. Intraluminal pressure was increased in steps between 0 and 90 mm Hg. The steady state diameter at each step was measured. These measurements were repeated in the presence of U46619, a thromboxane (TX) A2 receptor agonist (at a concentration of 10(-6) M), and bradykinin (BK; at 10(-6) M). Finally, Ca2+-free Krebs-induced passive diameter (PD) was measured in each group. Ovariectomy increased spontaneous myogenic tone of coronary arteries (p<0.05), which was normalized by estrogen replacement. Ovariectomy decreased distensibility observed at low pressure, although passive diameter was not changed. Estrogen replacement decreased wall stress and elastic modulus (p<0.05). The thromboxane A2 agonist induced the largest contraction in the ovariectomized group, whereas bradykinin-induced relaxation was the largest in the estrogen replacement group (p<0.05). Estradiol hormone replacement therapy (HRT) may exert a beneficial effect on myocardial perfusion in menopause by opposing the deterioration of biomechanical properties of intramural coronary resistance vessels induced by female sex hormone depletion.

The Effect of Ovariectomy and Long-term Estrogen Replacement on Bladder Structure and Function in the Rat

PURPOSE The use of estrogen replacement therapy for treating postmenopausal urinary incontinence is a controversial topic. We examined the behavioral, cystometric and histological changes that occur with long-term estrogen depletion and supplementation in rat bladders to determine the role of menopause in lower urinary tract dysfunction. MATERIALS AND METHODS A total of 40 female Sprague-Dawley rats were placed into 1 of 3 groups, including bilateral ovariectomy, bilateral ovariectomy plus estrogen replacement and control. The estrogen replaced group received a 0.25 mg. 16-week sustained release pellet (Innovative Research of America, Sanasota, Florida) placed subcutaneously. After surgery voiding frequency and volume were measured in 24-hour periods by placing animals in metabolic cages. After 16 weeks the rats underwent catheterization and continuous cystometry. The bladder was then removed and stained with Gomori trichrome. The collagen-to-smooth muscle density ratio was calculated for each specimen using current imaging software. RESULTS There was no significant difference in voiding patterns in the 3 groups, as measured by volume and voiding frequency. Cystometric data showed a trend toward higher voiding pressure, threshold pressure, baseline pressure and mean inter-voiding pressure in the ovariectomy group compared with the estrogen and control groups, although there was no statistical significance. Histological studies showed a higher mean collagen-to-smooth muscle ratio plus or minus standard deviation in the ovariectomy group (0.807 +/- 0.204) than in the ovariectomy plus estrogen replacement (0.709 +/- 0.118) and control (0.700 +/- 0.129) groups (p <0.05). Furthermore, when histological and cystometric data were compared for individual samples, we found a direct correlation of mean inter-voiding pressure (a measure of bladder instability) with the collagen-to-smooth muscle ratio (p <0.05). CONCLUSIONS Long-term estrogen replacement is beneficial for treating postmenopausal urinary incontinence.