Effect of estradiol on tissue glycogen metabolism in exercised oophorectomized rats

The effect of both physiological and pharmacological doses of estradiol on exercise performance and tissue glycogen utilization was determined in oophorectomized estradiol-replaced (ER) rats. Doses of beta-estradiol 3-benzoate (0.02, 0.04, 0.1, 0.2, 1, 2, 4, or 10 micrograms.0.1 ml of sunflower oil-1.100 g body wt-1) were injected 5 days/wk for 4 wk. Controls were sham injected (SI). After treatment, the animals were run to exhaustion on a motorized treadmill. ER animals receiving the 0.02-microgram dose ran significantly longer and completed more total work than the SI group. ER animals receiving doses of greater than or equal to 0.04 microgram ran longer and performed more work than the 0.02-microgram group. At exhaustion, myocardial glycogen content was significantly decreased in animals that were ER with less than or equal to 0.1 microgram, whereas those replaced with doses greater than 0.1 microgram utilized significantly less glycogen. With the 10-micrograms dose no significant decrease in heart glycogen content was observed at exhaustion. A submaximal 2-h run significantly reduced glycogen content in heart, red and white portions of the vastus lateralis, and the livers of SI animals. The latter effect was attenuated in skeletal muscle and liver, and there was no effect in the hearts of the ER animals receiving 2 micrograms. These data indicate that estradiol replacement in oophorectomized rats influenced myocardial glycogen utilization during exhaustive exercise and spared tissue glycogen during submaximal exercise. These glycogen sparing effects may have contributed to the significant improvements in exercise performance observed in this study.     

Resorption of collagen by hepatocytes during the reverse development of liver cirrhosis

Electron microscopy applied in experiments on white mice has demonstrated the presence of vacuoles containing collagen fibers in the cytoplasm of hepatocytes during reverse development of liver cirrhosis. As the organ regenerated, the number of vacuoles with decomposing collagen in the hepatocytes and the number of phagocytosing hepatocytes increased. Based on the data obtained the conclusion is made that during reverse development of liver cirrhosis one can observe the phenomenon of intracellular resorption of collagen by hepatocytes by means of collagen phagocytosis.     

Effects of exercise on insulin distribution and action in testosterone-treated oophorectomized female rats.

Administration of testosterone (T) to oophorectomized (Ovx) female rats is followed by severe insulin resistance, localized to postreceptor cellular events in the muscle. In this study, intervention by exercise was introduced to examine whether circulatory adaptations are involved in insulin resistance. Two groups of Ovx rats were studied: one group was given T (Ovx+T); another group had free access to running wheels (Ovx+T+Ex). In addition, one control group (sham operated) was studied. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp technique (submaximal) for 150 min. Muscle interstitial glucose and insulin concentrations were measured by microdialysis. The measurements showed that, in Ovx+T rats, the onset of insulin action was significantly (P < 0.05) slower during the first 95 min of the clamp compared with that in Ovx+T+Ex and controls. Muscle interstitial concentrations of insulin but not glucose were lower in both Ovx+T and Ovx+T+Ex rats than in controls throughout the clamp. It was concluded that physical exercise prevented the slow onset of insulin action in Ovx+T rats without changing the distribution time of muscle interstitial insulin. The results indicate that hyperandrogenicity is characterized by delayed muscle insulin action. Physical exercise reverses these defects without any beneficial effect on muscle interstitial insulin concentrations.     

Effect of dehydroepiandrosterone sulfate on carnitine acetyl transferase activity and l-carnitine levels in oophorectomized rats

Alteration in energy metabolism of postmenopausal women might be related to the reduction of dehydroepiandrosterone sulfate (DHEAS). DHEA and DHEAS decline with age, leveling at their nadir near menopause. DHEA and DHEAS modulate fatty acid metabolism by regulating carnitine acyltransferases and CoA. The purpose of this study was to determine whether dietary supplementation with DHEAS would also increase tissue l-carnitine levels, carnitine acetyltransferase (CAT) activity and mitochondrial respiration in oophorectomized rats. Plasma l-carnitine levels rose following oophorectomy in all groups (P<0.0001). Supplementation with DHEAS was not associated with further elevation of plasma l-carnitine levels, but with increased hepatic total and free l-carnitine (P=0.021 and P<0.0001, respectively) and cardiac total l-carnitine concentrations (P=0.045). In addition, DHEAS supplementation increased both hepatic and cardiac CAT activities (P<0.0001 and P=0.05 respectively). CAT activity positively correlated with the total and free carnitine levels in both liver and heart (r=0.764, r=0.785 and r=0.700, r=0.519, respectively). Liver mitochondrial respiratory control ratio, ADP:O ratio and oxygen uptake were similar in both control and supplemented groups. These results demonstrate that in oophorectomized rats, dietary DHEAS supplementation increases the liver and heart l-carnitine levels and CAT activities. In conclusion, DHEAS may modulate l-carnitine level and CAT activity in estrogen deficient rats. The potential role of DHEAS in the regulation of fatty acid oxidation in postmenopausal women is worthy of investigation.     

Effects of the beta3 adrenergic receptor agonist on developmental obesity in oophorectomized rats.

In this study, we evaluated the anti-obesity effects of selective beta3 adrenergic receptor agonist (ARa) and/or a diet in oophorectomized (OVX) treatment in obese rats. Ten-week-old female Sprague-Dawley rats were divided into 4 groups: (1) OVX; (2) OVX treated with beta3 ARa, BRL 35 135; (3) sham-operated controls (sham group); (4) sham-treated with beta3 ARa (sham+ARa group). These four groups were divided into two groups, one on ad libitum diet, and the other on a diet of limited chow. The effects of beta3 ARa on body weight, intraabdominal fat weight, adipocyte volume, serum lipid content, and serum leptin were measured after 4 weeks had been completed. On both the ad libitum and the limited diet, ARa significantly reduced the ratio of intraabdominal fat and body weight (IAF ratio) regardless whether in the OVX or sham group, although ARa had no influence on weight gain. On the ad libitum diet, the serum leptin was significantly increased after OVX, and significantly reduced after ARa administration. ARa significantly reduced the volume of intraabdominal adipocytes. We conclude that ARa reduces intraabdominal fat without reducing body weight in oophorectomized rats. The serum parameter affected differently to rats on the ad libitum diet and on the limited diet.     

Muscle collagen content in diabetic rats

Collagen content (mg/dl of dry weight) was measured biochemically in the extensor digitorum longus and the soleus muscle in rats. Comparison of muscles from diabetic (induced by intraperitoneal streptozotocin injection /60 mg/kg body weight/) and non diabetic controls showed an increase in the collagen content of the extensor digitorum longus, and little change in the soleus. The differences did not attain statistical significance indicating that the accelerated collagen ageing attributed to diabetes may not necessarily be true in all tissues.     

Spontaneous endometrial tumours of 'Sabra' rats

In a 2 year study of 171 female (101 virgin; 70 multiparous) 'Sabra' rats, spontaneous endometrial tumours were found in 69% of 2 year old animals. Tumour development appeared to be age related, and only virgin females showed tumours before 18 months of age. Polyps were the most prevalent tumour type, followed by adenocarcinomas. The Sabra rat can be included among those rat strains having a high incidence of spontaneous endometrial neoplasia.     

Cellular sensitivity to collagen in bleomycin-treated rats

Previous reports have suggested that immune mechanisms are involved in the induction of certain types of pulmonary fibrosis. In this study endotracheal bleomycin was used to induce pulmonary fibrosis in rats, and they were then examined for cellular sensitivity to homologous interstitial collagens isolated from lung. Results indicate that rats treated with bleomycin develop transient cellular sensitivity to homologous collagen. Immunity appears to be selective to type I collagen with minimal response to type III collagen. The kinetics of the development of autoimmunity paralleled the transient increase in collagen synthesis in response to bleomycin treatment. This response was abolished upon prior treatment of the challenging antigen with purified bacterial collagenase, but was resistant to trypsin digestion. This finding confirms the true collagenous nature of the stimulating antigen and eliminates the possibility of a noncollagenous contaminant as the effective agent in the antigen preparation. The data suggest that cellular sensitivity to homologous collagen in response to bleomycin treatment may play a role in the overall fibrotic response.     

Transendothelial channels in fenestrated endometrial blood capillaries of rats

Summary Three types of transendothelial channels are described in the endothelium of blood capillaries in the endometrium of the rat. It is postulated that they may function as pores draining interstitial fluid to the venous blood.Supported by a grant from the Nationaal Fonds voor Wetenschappelijk Onderzoek — Fonds voor Geneeskundig Wetenschappelijk Onderzoek (Belgium)     

Loss of collagen type VI from rat endometrial stroma during decidualization.

The expression of collagen type VI in the extracellular matrix of rat uterine endometrial stroma after a decidual stimulus was examined by immunolocalization and immunoblotting. The intermediate filament protein, desmin, was used as a marker to identify decidual cells. Tissue was examined from pregnant animals and from ovariectomized, hormone-treated rats in which decidualization had been induced artificially. In undifferentiated tissue from both groups of animals, collagen type VI was abundant, and desmin was present only in vascular smooth muscle cells. By 72 h after a decidual stimulus, however, collagen type VI had essentially disappeared from the matrix of the antimesometrial stromal compartment, and desmin was highly expressed in the decidualizing cells. During regression of the decidual tissue, collagen type VI began to reappear in the stromal matrix, whereas desmin expression declined as decidual cells degenerated. These results indicate that remodeling of the uterine extracellular matrix in response to embryo implantation is a function of the differentiating decidual cell.     

Increased degradation of dermal collagen in diabetic rats.

The effect of alloxan induced diabetes on the dermal collagen content of albino rats was studied in relation to few lysosomal enzymes. Diabetes decreased the dermal collagen content. The specific activities of the lysosomal enzymes studied in the diabetic rat skin were elevated. It has been established that lysosomal enzymes degrade the connective tissue components. Thus, it may be suggested that the increase in the lysosomal enzymes studied should have facilitated the decrease in dermal collagen content of diabetic rats by increasing the degradation of dermal collagen.     

瘦素促进皮肤创伤大鼠胶原合成的实验研究

目的：研究瘦素对创伤大鼠创面组织胶原合成的影响,探讨瘦素促进创伤愈合的作用机制。方法：雄性Wistar大鼠30只,体质量（180±20）g,按体重随机分为：正常组、创伤对照组和瘦素治疗组,用5%Na2S背部脱毛。瘦素治疗组和创伤对照组大鼠于背部制做缺损创面（2.0 cm×2.5 cm）,并分别用瘦素蛋白溶液0.1 ml（含瘦素2.0μg）和等体积生理盐水涂抹,每天一次,连续7 d。之后处死大鼠,取创面组织及正常组大鼠相应部位脱毛皮肤检测皮肤及创面胶原合成相关指标。结果：瘦素治疗组肉芽组织中羟脯氨酸含量（33.92±3.09）mg/g较创伤对照组（29.55±3.59）mg/g显著升高（P〈0.05）,I、Ⅲ型胶原mRNA的水平0.96±0.09、0.09±0.06分别较创伤对照组0.80±0.03、0.08±0.03显著增加（P〈0.05）,I、Ⅲ型胶原的蛋白表达也较创伤对照组显著增强。结论：瘦素通过促进创伤组织I、Ⅲ型胶原的基因表达和胶原蛋白的合成,从而加快肉芽组织的生长,促进创伤组织的修复和愈合。