Effects of ovariectomy on thermogenesis in brown adipose tissue and liver in Syrian hamsters

Weight gain in ovariectomized Syrian hamsters occurs without increased food intake, which suggests that metabolic efficiency may be enhanced through a reduction in energy expenditure. We examined the effect of ovariectomy on metabolic activity in brown adipose tissue and liver. Four groups of hamsters (n = 13, each) were killed 0, 2, 4, or 16 weeks following ovariectomy. Ovariectomized hamsters rapidly gained weight without overeating. Body weights stabilized after 8 weeks and remained 12-17% above sham-operated control weights for the duration of the experiment. Weight gain in the hamsters ovariectomized for 16 weeks was characterized by significant increases in retroperitoneal white adipose tissue weight and carcass lipid content. Similar trends were seen in 2-week and 4-week ovariectomized animals. There were no differences in interscapular brown adipose tissue weight, protein content, DNA content, or norepinephrine (NE) content among sham-operated and 2-, 4-, or 16-week ovariectomized hamsters, indicating that ovariectomy had no effect on brown adipose tissue growth. Similarly, there was no difference in either sympathetic nervous system activity (estimated by the rate of NE turnover) or mitochondrial GDP binding among the four groups of hamsters. In contrast, hepatic cytochrome P-450 activity was significantly reduced 2, 4, and 16 weeks after ovariectomy. These results suggest that reduced thermogenic activity in liver, but not in brown adipose tissue, could contribute to the weight gain in Syrian hamsters after ovariectomy.     

Ovarian hormone effects on activity, glucoregulation and thyroid hormones in the rat

Ovarian hormonal influences on the range of physiological and behavioral variables which combine to affect overall energy balance are poorly delineated. In the present study 4 groups of virgin, female rats (intact, ovariectomized, ovariectomized with estrogen replacement and ovariectomized with estrogen plus progesterone) were allowed access to running wheels and activity; food intake and weight gain were measured initially under food restricted, then under ad lib conditions. Serum insulin, glucose, thyroxine (T4) and triiodothyronine (T3) were determined on trunk blood samples obtained at the end of the experiment. Ovariectomy resulted in an increased rate of weight gain through reduced activity and T3 but food intake was unchanged. Insulin levels were greatly reduced. Estrogen replacement restored activity to the intact group's level and normalized weight gain. Insulin and T3 were also raised to control levels but T4 was reduced as was serum glucose. Estrogen plus progesterone replacement reduced weight gain markedly and increased T3 with normal T4. Despite the lower body weight this group was hyperglycemic and hyperinsulinemic suggesting insulin resistance. The results have important implications for the glucoregulatory and energy balance perturbations of ovarian hormone fluctuations and focus particularly on progesterone.     

The effects of estradiol on body weight and food intake in normal weight VMH-lesioned rats.

The effects of estradiol on food intake and body weight were examined in ovariectomized and VMH-lesioned, ovariectomized rats that were prevented from supranormal weight gain by food restriction. Estradiol injections that were effective in reducing weight in supranormal weight, ovariectomized rats had no effect on weight in normal weight, ovariectomized or VMH-lesioned, ovariectomized rats. Estradiol did not prevent hyperphagia and weight gain in VMH-lesioned, ovariectomized rats when they were provided with ad lib food.     

The significance of decreased ambulatory activity during the generation by long-term observation of obesity in ovariectomized rats

We attempted to determine the significance of ambulatory activity as a cause of overweight in ovariectomized rats. Drinking and ambulation were measured continuously and directly for periods up to 12 months in special apparatus developed at Gunma University. In older rats, ambulatory activity decreased much more in the ovariectomy group than in the control group. There was no difference in food intake between the ovariectomized and the control group. After 2 months, the ovariectomy group increased body weight more than the control group despite no difference in food intake. The decrease in ambulatory activity was consistent in the ovariectomy group, regardless of any differences in age and body weight. These results indicate that decrease of energy expenditure by gradual decrease in ambulatory activity may be an important factor as a cause of overweight in ovariectomized, obese rats.     

Dehydroepiandrosterone-dependent induction of peroxisomal proliferation can be reduced by aspartyl esterification without attenuation of inhibitory bone loss in ovariectomy animal model

The purpose of this study was to determine whether esterification of dehydroepiandrosterone with aspartate (DHEA-aspartate) could reduce peroxisomal proliferation induced by DHEA itself, without loss of antiosteoporotic activity. Female Sprague-Dawley rats were ovariectomized, then DHEA or DHEA-aspartate was administered intraperitoneally at 0.34 mmol/kg BW 3 times a week for 8 weeks. DHEA-aspartate treatment in ovariectomized rats significantly increased trabeculae area in tibia as much as DHEA treatment. Urinary Ca excretion was not significantly increased by DHEA or DHEA-aspartate treatment in ovariectomized rats, while it was significantly increased by ovariectomy. Osteocalcin concentration and alkaline phosphatase activity in serum and cross linked N-telopeptide type I collagen level in urine were not significantly different between DHEA-aspartate and DHEA treated groups. DHEA-aspartate treatment significantly reduced liver weight and hepatic palmitoyl-coA oxidase activity compared to DHEA treatment. DHEA-aspartate treatment maintained a nearly normal morphology of peroxisomes, while DHEA treatment increased the number and size of peroxisomes in the liver. According to these results, it is concluded that DHEA-aspartate ester has an inhibitory effect on bone loss in ovariectomized rats with a marked reduction of hepatomegaly and peroxisomal proliferation compared to DHEA.     

Food intake and adipose tissue lipoprotein lipase activity after hypothalamic estradiol benzoate implants in rats

Unilateral implants of estradiol benzoate in the ventromedial hypothalamus (VMH) reduced food intake in ovariectomized rats. The implants did not produce cornification of the vaginal epithelium. Furthermore, the reduction in food intake was observed in the absence of changes in adipose tissue lipoprotein lipase activity or cytoplasmic progestin receptor levels. These results suggest that, while estradiol may normally act at both central and peripheral sites to affect food intake and body weight, estrogenic stimulation of just the VMH may be sufficient to reduce food intake in ovariectomized rats.     

Ovarian influences on body weight regulation in rats with lateral hypothalamic lesions

The effect of lateral hypothalamic lesions upon the level of maintained body weight was studied in gonadally intact and ovariectomized female rats. The body weight of both the gonadally intact and ovariectomized animals declined after lesioning; but, while the weight level of the ovariectomized animals remained approximately 10% below normal, the body weight of the intact group steadily approached that of nonlesioned controls. This result suggests that ovarian factors contribute to the smaller effect on body weight as reported by others for females with lateral hypothalamic lesions. Further support for this hypothesis was found in the observations that (1) the reduced effect of lateral hypothalamic lesions on body weight of gonadally intact females was associated with prolonged periods of diestrus and (2) the normal weight suppressing effects of estrogen were attenuated by lateral hypothalamic lesions in the ovariectomized animals.     

Effects of voluntary exercise on sexual behavior in female rats

In two experiments, ovariectomized rats given access to activity wheels showed significantly higher lordosis ratings following estradiol treatment than animals maintained in individual hanging cages. Estrogen-induced decreases in body weight also were greater in wheel-housed animals. We suggest that access to running wheels may alter responsiveness to estradiol.     

六月龄大鼠去卵巢后建立骨质疏松症模型的可行性

背景：目前关于鼠龄对去势雌性大鼠建立骨质疏松模型影响的报道较少。 目的：验证6月龄大鼠去卵巢对构建骨质疏松症模型的可行性。 方法：6月龄雌性大鼠48只,分为2组,去卵巢组摘除双侧卵巢建立大鼠骨质疏松模型,假手术组不摘除卵巢,切除卵巢周围少量脂肪组织。建模后1,2,3个月测定大鼠体质量、子宫湿质量、碱性磷酸酶、抗酒石酸酸性磷酸酶、骨矿密度和骨矿含量等指标变化。 结果与结论：建模后1,2,3个月,去卵巢组比假手术组大鼠体质量明显增加(P < 0.05),子宫湿质量较假手术组量明显下降(P < 0.05)。建模后1个月,去卵巢组大鼠血清碱性磷酸酶指标显著高于假手术组(P < 0.05);建模后3个月,去卵巢组抗酒石酸酸性磷酸酶指标显著高于假手术组(P < 0.05);碱性磷酸酶指标和抗酒石酸酸性磷酸酶指标随大鼠月龄增加有轻度增高趋势。建模后2,3个月去卵巢组骨矿密度显著低于假手术组(P < 0.05)。表明6月龄大鼠去卵巢可成功建立骨质疏松症模型。     

Ovarian modulation of lipoprotein lipase activity in white adipose tissue of ground squirrels

Golden-mantled ground squirrels were ovariectomized (OVX) or Sham-OVX during the weight gain phase of the circannual body weight cycle. Other squirrels, OVX or Sham-OVX during the weight loss phase, were subcutaneously implanted with estradiol-filled or empty Silastic capsules. The mass of several fat pads as well as adipose tissue lipoprotein lipase (LPL) activity were determined at autopsy. Ovariectomy at either phase of the annual cycle was without effect on body weight. However, LPL activity of the parametrial fat pad was increased in OVX as compared to Sham-OVX squirrels. Fourteen days of estradiol treatment during the weight loss phase decreased the mass and LPL activity of the retroperitoneal fat depot but did not affect these parameters in perirenal adipose tissue. Although estradiol exerts different or opposite effects on body mass and food intake of rats and ground squirrels, ovariectomy and estrogen treatment affect LPL activity in a similar fashion in both species.     

Differential effect of oestrogen on post-exercise cardiac muscle myeloperoxidase and calpain activities in female rats

The effects of oestrogen administration on 1 h post-exercise cardiac muscle myeloperoxidase (MPO) and calpain activities were determined in female rats. Rats were ovariectomized and implanted for 2 weeks with either oestrogen (25 mg 17-oestradiol) or placebo pellets or left with ovaries intact. Rats were then run for 1 h at 21 m min-1, 12% grade, killed 1 h post-exercise and cardiac muscle and blood samples were removed. Control animals from each group were killed without prior exercise. Serum oestrogen levels in the order of the highest to lowest were; ovariectomized oestrogen replaced rats > intact ovaries rats > ovariectomized placebo rats. Oestrogen induced significant (P < 0.05) elevations in cardiac MPO activity at rest and at 1 h post-exercise in ovariectomized rats. No significant elevations in cardiac MPO activity were evident in placebo ovariectomized or normal ovary rats at rest or post-exercise. Cardiac calpain activities were similar in all unexercised groups. Ovariectomized placebo and intact ovary rats had significantly (P < 0.05) elevated cardiac calpain activities 1 h post-exercise while calpain activity was not significantly elevated in hearts from ovariectomized oestrogen rats. These results demonstrate that oestrogen supplementation in ovariectomized rats induces elevations in cardiac muscle MPO activities at rest and at 1 h post-exercise. This is opposite to the effect of oestrogen in post-exercise skeletal muscle and implies a greater neutrophil infiltration into cardiac muscle caused by oestrogen. This effect cannot be explained by changes in 1 h post-exercise cardiac muscle calpain activity, the elevation of which was suppressed by oestrogen administration. Oestrogen influences cardiac calpain activity similarly to its effect in skeletal muscle. Thus, oestrogen administration to ovariectomized rats induces elevations in cardiac MPO activity while suppressing cardiac calpain activity.     

Differential effect of oestrogen on post‐exercise cardiac muscle myeloperoxidase and calpain activities in female rats

The effects of oestrogen administration on 1 h post‐exercise cardiac muscle myeloperoxidase (MPO) and calpain activities were determined in female rats. Rats were ovariectomized and implanted for 2 weeks with either oestrogen (25 mg 17‐oestradiol) or placebo pellets or left with ovaries intact. Rats were then run for 1 h at 21 m min^–1, 12% grade, killed 1 h post‐exercise and cardiac muscle and blood samples were removed. Control animals from each group were killed without prior exercise. Serum oestrogen levels in the order of the highest to lowest were; ovariectomized oestrogen replaced rats > intact ovaries rats > ovariectomized placebo rats. Oestrogen induced significant (P < 0.05) elevations in cardiac MPO activity at rest and at 1 h post‐exercise in ovariectomized rats. No significant elevations in cardiac MPO activity were evident in placebo ovariectomized or normal ovary rats at rest or post‐exercise. Cardiac calpain activities were similar in all unexercised groups. Ovariectomized placebo and intact ovary rats had significantly (P < 0.05) elevated cardiac calpain activities 1 h post‐exercise while calpain activity was not significantly elevated in hearts from ovariectomized oestrogen rats. These results demonstrate that oestrogen supplementation in ovariectomized rats induces elevations in cardiac muscle MPO activities at rest and at 1 h post‐exercise. This is opposite to the effect of oestrogen in post‐exercise skeletal muscle and implies a greater neutrophil infiltration into cardiac muscle caused by oestrogen. This effect cannot be explained by changes in 1 h post‐exercise cardiac muscle calpain activity, the elevation of which was suppressed by oestrogen administration. Oestrogen influences cardiac calpain activity similarly to its effect in skeletal muscle. Thus, oestrogen administration to ovariectomized rats induces elevations in cardiac MPO activity while suppressing cardiac calpain activity.     

Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cII gene of transgenic big blue rats

A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats.     

The effect of supplemental copper on osteopenia induced by ovariectomy in rats

OBJECTIVE: The effect of a copper supplement on preventing bone mass loss induced by ovariectomy in rats was investigated. DESIGN: Three groups of fifteen 100-day-old female Wistar rats, each with a mean initial weight of approximately 260 g per animal, were selected for a 30-day experiment. One group of 15 ovariectomized rats was fed a diet supplemented with 15 mg of copper per kilogram of feed. The other two groups: 15 ovariectomized and 15 Sham- ovariectomized rats did not receive the supplement. Morphometric (weight and length) and densitometric studies with dual-energy x-ray absorptiometry were performed on the whole femur and the fifth lumbar vertebra of each animal at the end of the 30-day period. RESULTS: The ovariectomized rat group fed a diet supplemented with copper did not show the bone mass loss at the axial (fifth lumbar vertebra) or peripheral (femur) level that was evidenced in the ovariectomized group. CONCLUSIONS: The results of the measurement of axial and peripheral bones show that a supplement of copper may have a potential therapeutic application in the treatment and prevention of involutional osteoporosis.     

Use of running wheels regulates the effects of the ovaries on circadian rhythms.

Free-running circadian rhythms in core temperature, wheel-running and general locomotor activity were studied in ovariectomized or intact female rats housed with or without access to a running wheel. No differences in the monitored parameters were found between the intact and ovariectomized rats without a wheel. In the presence of a wheel, however, the intact rats differed from those that had been ovariectomized by displaying a shorter circadian period, an increased amplitude of the temperature rhythm, and strikingly higher rates of wheel-running and general locomotor activity. After estradiol treatment, the ovariectomized rats with a wheel developed a small increase in the temperature amplitude, and also in the correlation between wheel-running and general locomotor activity; these changes were not associated with a significant increase in wheel-running or a shortening of the circadian period. We conclude that some of the differences in circadian function between intact and ovariectomized rats are due to the differential use they make of running wheels, when available, and not directly attributable to the absence or presence of gonadal steroids.     

雌二醇对大鼠细胞免疫功能 的影响

本文采用大鼠去卵巢或再补充雌二醇(E_2)的方法探讨 E_(2)对免疫器官及其细胞免疫功能的影响。结果表明,去卵巢大鼠的脾脏和胸腺肥大,重量增加,脾细胞和胸腺细胞数明显增多。给去卵巢大鼠补充 E_2可使上述变化逆转。切除卵巢后的大鼠脾细胞对 ConA 诱导的增殖应答反应和诱生 IL—2的能力明显增高,补充 E_(2)亦可使上述变化逆转。但去卵巢大鼠的胸腺细胞对 ConA 诱导的增殖应答反应未能检测到可见的变化;给去卵巢鼠补充 E_2后,胸腺细胞对 ConA 的应答反应反而增强,并观察到胸腺细胞呈现轻度的自发增殖反应。实验结果表明:E_2能影响外周和中枢免疫器官及其细胞免疫功能,但这种影响在外周和中枢免疫器官表现出不同的变化。     

The luteinizing hormone releasing activity of extracts of blood from the hypophysial portal vessels of rats

1. A method of acid ethanol extraction and gel filtration was used to obtain a `luteinizing hormone (LH)-free' fraction of blood collected from the cut pituitary stalk of rats (termed hypophysial portal blood).

2. The `LH-free' fraction of hypophysial portal plasma from hypophysectomized and from ovariectomized rats caused a greater depletion of ovarian ascorbic acid in immature rats, pretreated with gonadotrophins, than a similar fraction of systemic plasma obtained from the same donor animals.

3. The `LH-free' fraction of hypophysial portal plasma from ovariectomized rats evoked a rise in the level of LH in the systemic plasma of ovariectomized, oestrogen and progesterone treated, rats. This fraction also caused ovulation in rabbits when infused directly into the anterior pituitary gland of these animals. The activity of the `LH-free' fraction of systemic plasma was considerably less than that of portal plasma in either of these assay systems.

4. The results of these experiments suggest the presence of a factor in the `LH-free' fraction of hypophysial portal plasma which is capable of causing the release of luteinizing hormone from the anterior pituitary gland. The molecular weight of this factor, as assessed by its behaviour on filtration through `Sephadex G-25', is probably less than 5000.

5. The LRF activity of the `LH-free' fraction of hypophysial portal plasma obtained from rats at various phases of the oestrous cycle was measured by the ovarian ascorbic acid depletion method. There appears to be a decrease in the level of activity at oestrus. However, a rise in LRF activity, which was expected to occur at the `critical period' of prooestrus, was not evident. The significance of these findings is discussed.

     

Role of gonadal hormones in diet selection and food utilization in female rats

Patterns of dietary self-selection were examined in ovariectomized and sham-operated female rats. Self-selection animals were offered separate dietary sources of protein, carbohydrate, and fat. Control animals were offered ground Purina Rodent Chow. Food intakes, water intakes, and body weights were measured daily for all animals. During a 19-day baseline period, selecting animals chose approximately one third of their daily caloric intake from each of the three diet sources. Following this baseline period, half of the self-selection animals and half of the control animals received bilateral ovariectomies, while the remaining animals in each diet group received sham-operations. Following ovariectomies, both self-selection and control animals significantly increased food intakes and rate of weight gains above baseline values. In contrast, sham-operated animals did not increase food intakes or rate of weight gain following surgery. When weight gain was calculated as a function of caloric intake, ovariectomized animals gained nearly twice as much weight per kilocalorie consumed as sham-operated animals. Ovariectomized animals showed no changes in diet selection after surgery, while sham-operated animals showed a slight decrease in the percentage protein selected. Differences between self-selection patterns in ovariectomized animals and in animals with other forms of experimentally-induced obesity suggest distinct metabolic patterns may underlie various forms of obesity.     

Effects of estrous cycles and ovarian steroids on body weight and energy expenditure in Syrian hamsters

In Experiment 1, highly significant changes were observed over the estrous cycle in body weight gain, but not in food intake, daytime resting oxygen consumption or brown fat thermogenesis in Syrian hamsters. In Experiments 2 and 3, body weight and composition, food intake, resting oxygen consumption, and brown fat thermogenesis were measured following estradiol or estradiol plus progesterone treatment in ovariectomized hamsters. The significant changes in body weight could not be explained by changes in food intake, and were not accompanied by significant alterations in daytime oxygen consumption or brown fat thermogenic activity. In Experiment 4, resting oxygen consumption and body weight were measured every 6 hours over the estrous cycle. There was a striking absence of the usual nocturnal peak in resting oxygen consumption on the night of estrus (the night of the largest body weight gain). However, brown fat thermogenic activity did not differ among groups of hamsters killed on different nights of the estrous cycle. Estradiol-induced changes in energy storage may be mediated by changes in the daily rhythm of energy expenditure which are not dependent on alterations in brown fat thermogenesis.