DIFFERENTIAL EFFECTS OF OESTRADIOL AND ETHYNYL OESTRADIOL ON LIPID METABOLISM IN THE FEMALE RAT

1978 ◽  
Vol 79 (3) ◽  
pp. 405-406 ◽  
Author(s):  
A. VALETTE ◽  
G. CARASCO ◽  
A. VÉRINE ◽  
L. VARÉSI ◽  
J. BOYER

Service d'Explorations Métaboliques, Hôpital de la Conception, 13385 Marseille Cedex 4, France (Received 24 July 1978) It has recently been shown that ethynyl oestradiol markedly decreases lipase activity in the liver (Valette, Verine, Salers & Boyer, 1977). These observations, along with reports of oestrogen receptors in the liver (Chamness, Costlow & McGuire, 1975) suggest that oestrogens exert considerable influence over the hepatic metabolism of lipids. Previous investigations (DeLorimier, Gordon, Lowe & Carbone, 1965; Gallagher, Mueller & Kappas, 1966) have suggested that the extent of the hepatic changes could be correlated with the molecular nature of the hormonal compound and might depend particularly on the 17α-alkyl-substituted group in synthetic oestrogens. The influence of the ethynyl function in the 17α-position of oestradiol-17β on the oestrogen-induced changes observed in hepatic lipases and serum levels of triglycerides has therefore been examined. Adult female Sprague–Dawley rats (220–240 g) were allowed free access to food and

2001 ◽  
Vol 79 (6) ◽  
pp. 519-532 ◽  
Author(s):  
Clare L Ritter ◽  
William F Prigge ◽  
Mark A Reichert ◽  
Danuta Malejka-Giganti

Altered cytochrome P450-catalyzed metabolism of 17β-estradiol (E2) and estrone (E1) in the liver and (or) extrahepatic tissues may affect estrogen-sensitive tumorigenesis. We examined the effects of oral treatments of (i) indole-3-carbinol (I3C) at 250 or 500 mg/kg or β-naphthoflavone (β-NF) at 40 mg/kg of body weight (bw)/day from 51 to 54 days of age (acute regimen), and (ii) I3C at 250 mg/kg or β-NF at 20 mg/kg bw given 3x/week from 10 to 22 weeks of age (chronic regimen) in female Sprague-Dawley rats. We determined the effects of these treatments on the P450 content and P450 (CYP)-specific activities in the liver, P450-dependent metabolism of E2 and E1 by the liver and mammary gland, and interconversion of E1 and E2 catalyzed by 17β-hydroxysteroid dehydrogenase (17β-HSD) in these tissues and malignant mammary tumors. I3C at the two levels of acute regimen elicited similar responses. Acute and chronic treatments with I3C, but not β-NF, increased P450 content ~2-fold. I3C, and to a lesser extent β-NF, increased CYP1A1 and CYP1A2 probe activities in liver up to 117- and 27- fold, respectively, and after acute regimens, that of CYP3A by ~1.8-fold. I3C also increased activity of CYP2B up to 100-fold. Overall hepatic metabolism of E2 and E1, which was ~2-fold greater at 55 than 155 days of age, was increased (~2.8-fold) by I3C with 2-, 4-, 16α-, 6α-, 6β-, and 15α-hydroxy (OH) comprising [Formula: see text]54, 3, 2, ~2, ~5, 7, and 2%, respectively, of E1 and E2 metabolites. Acute regimens of β-NF increased 2- and 15α-OH-E2 (62 and 5% of total) from E2 and 2-, 4-, and 6α-OH-E1 + 6β-OH-E1 (32, 13, and 4% of total) from E1. Mammary gland metabolized E2 to E1 and small amounts of 15α-, 4-, 16α-, 6β-, and 6α-OH-E2. After the acute IC3 regimen, E2 was also converted to 2-OH-E2. 17β-HSD-catalyzed oxidation of E2 was favored in the liver and reduction of E1 was favored in mammary gland and tumor (= 1% of hepatic activity). An increased (~2-fold) ratio of reductive to oxidative activities in malignant mammary tumors by chronic I3C regimen may stimulate tumor growth. This is the first report showing that after chronic oral regimens, the I3C-, but not β-NF-, induced changes in CYP complement led to elevated E2 and E1 metabolism. The persistent effects of increased putative carcinogenic and estrogenic 4- and 16α-OH as well as 6α- and 6β-OH-E2 and 6β-OH-E1 might counteract those of the less estrogenic 2-OH metabolites, thus accounting for the lack of suppression of mammary tumorigenesis by I3C in our previous study.Key words: estrogen metabolism, P450, 17β-hydroxysteroid dehydrogenase, indole-3-carbinol, β-naphthoflavone.


2021 ◽  
pp. 1-21
Author(s):  
M.E. Ragi ◽  
R. El-Haber ◽  
F. El-Masri ◽  
O.A. Obeid

Abstract The ingestion of non-caloric sweeteners from food and/or drink was intended to reduce caloric intake without compromising palatability. However, the inconclusive relation between non-caloric sweeteners and body weight may partially relate to their form of ingestion (solid or liquid). Thus, two paralleled experiments (Aspartame and Sucralose) were conducted. In each, Sprague Dawley rats (7-week-old male) were randomly divided into 4 groups. In experiment 1, aspartame (0.05%) was added to the diet (AD) or drinking water (AW) or both diet and water (ADW), and a control group (C) was given a non-sweetened diet with plain water. In experiment 2, sucralose (0.016%) was similarly provided in the diet (SD) or drinking water (SW) or both diet and water (SDW), with a control group (C). All rats had free access to food and water for 7 weeks. Energy intake, body weight, and body composition were monitored and blood metabolites were determined. Results showed that aspartame ingestion significantly increased body weight and fat mass mainly due to an increase in energy efficiency. The effect was related to the amount rather than the form of ingestion. Additionally, aspartame ingestion was associated with glucose intolerance. Sucralose ingestion had a similar impact to that of aspartame though to a lesser extent. In conclusion, 7-week ingestion of aspartame and sucralose had adverse effects on body measures that were not related to the form of ingestion.


2019 ◽  
Vol 53 (3) ◽  
pp. 139-145
Author(s):  
Tolulope Oyesola ◽  
Bolanle Iranloye ◽  
Olufeyi Adegoke

AbstractObjective. This study was designed to investigate the effect of sublethal doses (10, 60, and 120 mg/kg of pirimiphos-methyl on implantation and pregnancy in female Sprague-Dawley rats. Pirimiphos-methyl is a pesticide widely used worldwide, especially in Africa to protect food against pests and has gained widespread acceptance.Methods. Pregnant Sprague-Dawley rats used for this study had access to food and water ad libitum and were divided into a control group and three experimental groups based on dose of chemical given. The pregnant rats were given pirimiphos-methyl orally on days 1–5, 1–7, 7–18th day of gestation and from day 1 to term. Implantation studies were carried out on days 6 and 8 of pregnancy, while the fetal parameters were ascertained on day 19 of pregnancy and at term. Serum levels of progesterone and estradiol were measured on days 6, 8 and 19 of pregnancy.Results. Sublethal administration of pirimiphos-methyl showed decreased number of implantation sites on days 6 and 8, fetal weight, crown-to-rump length, length of umbilical cord and placenta weight (day 19), birth weight, litter size and total number (at term) in rats administered with pirimiphos-methyl when compared with control.Conclusion. Administration of pirimiphos-methyl resulted in a reduced implantation rate due to decreased uterine receptivity caused by an imbalance in the level of estradiol and progesterone and impaired reproductive outcome during pregnancy.


2009 ◽  
Vol 106 (3) ◽  
pp. 911-918 ◽  
Author(s):  
Zongjian Zhu ◽  
Weiqin Jiang ◽  
John N. McGinley ◽  
Henry J. Thompson

The objective of this experiment was to determine the effects on mammary carcinogenesis of similar limitations in energy availability either by energy expenditure due to moderate-intensity running (physical activity, PA) or by regulating dietary energy (RE) intake relative to a sedentary control (SC) group that ate ad libitum. A total of 90 female Sprague-Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either SC, a PA group given free access to a motorized running wheel, or a RE group whose food intake limited growth to the rate observed in PA. Compared with SC, mammary carcinogenesis was inhibited by RE or PA. Cancer incidence, 92.6%, 77.8%, and 66.7% ( P = 0.06), and cancer multiplicity, 3.44, 2.11, and 1.62 cancers/rat ( P = 0.006), in SC, RE, and PA, respectively, were reduced to a similar extent by RE and PA. Histological and Western blot analyses of mammary carcinomas provided evidence that RE and PA induced apoptosis via the mitochondrial pathway, that cell cycle progression was suppressed at the G1/S transition, and that intratumoral blood vessel density was reduced, although it remains to be determined whether PA and RE exert these effects via the same mechanisms.


1974 ◽  
Vol 75 (3) ◽  
pp. 491-496 ◽  
Author(s):  
Junichi Mori ◽  
Hiroshi Nagasawa ◽  
Reiko Yanai ◽  
Junji Masaki

ABSTRACT The sequence of changes in the serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from 2 days before to 24 h after parturition of primiparous Sprague-Dawley rats was investigated by radioimmunoassay. No appreciable change in average serum FSH levels was observed during 2 days before and 1 h after parturition. After this the levels increased gradually to show a peak at 7 h after parturition and then declined gradually until 24 h after parturition. However, the level at 24 h after parturition was still twice as high as that at parturition (0 h). The average serum LH levels which were low between 2 days before and 1 h after parturition, showed a peak at 7 h and decreased toward 13 h after parturition. The same levels as at parturition were maintained between 13 and 24 h after parturition. The time of surge of either FSH or LH was closely related to the time after parturition. There were some differences between FSH and LH in the patterns of sequence of changes in the serum levels near parturition.


2009 ◽  
Vol 87 (6) ◽  
pp. 460-470 ◽  
Author(s):  
Claude Lajoie ◽  
Viviane El-Helou ◽  
Cindy Proulx ◽  
Robert Clément ◽  
Hugues Gosselin ◽  
...  

Rapamycin represents a recognized drug-based therapeutic approach to treat cardiovascular disease. However, at least in the female heart, rapamycin may suppress the recruitment of putative signalling events conferring cardioprotection. The present study tested the hypothesis that rapamycin-sensitive signalling events contributed to the cardioprotective phenotype of the female rat heart after an ischemic insult. Rapamycin (1.5 mg/kg) was administered to adult female Sprague–Dawley rats 24 h after complete coronary artery ligation and continued for 6 days. Rapamycin abrogated p70S6K phosphorylation in the left ventricle of sham rats and the noninfarcted left ventricle (NILV) of 1-week postmyocardial-infarcted (MI) rats. Scar weight (MI 0.028 ± 0.006, MI+rapamycin 0.064 ± 0.004 g) and surface area (MI 0.37 ± 0.08, MI+rapamycin 0.74 ± 0.03 cm2) were significantly larger in rapamycin-treated post-MI rats. In the NILV of post-MI female rats, rapamycin inhibited the upregulation of eNOS. Furthermore, the increased expression of collagen and TGF-β3 mRNAs in the NILV were attenuated in rapamycin-treated post-MI rats, whereas scar healing was unaffected. The present study has demonstrated that rapamycin-sensitive signalling events were implicated in scar formation and reactive fibrosis. Rapamycin-mediated suppression of eNOS and TGF-β3 mRNA in post-MI female rats may have directly contributed to the larger infarct and attenuation of the reactive fibrotic response, respectively.


1995 ◽  
Vol 269 (5) ◽  
pp. R1174-R1178 ◽  
Author(s):  
J. L. Beverly ◽  
M. F. Beverly ◽  
M. M. Meguid

gamma-Aminobutyric acidergic (GABA) mechanisms in the ventral hypothalamus may be involved in counterregulatory responses to glucoprivic episodes. Microdialysis probes (1 mm) were placed into the ventromedial hypothalamus (VMH) or lateral hypothalamus (LHA) of male Sprague-Dawley rats 3.5 h before 2-deoxy-D-glucose (2-DG) administration (200 mg/kg i.v.). Probes were perfused (2 ml/min) with Ringer solution, and samples were collected every 10 min from 30 min before to 60 min after 2-DG. By 30 min after 2-DG, GABA concentration in VMH dialysate increased in a bimodal fashion to 204 +/- 36% (P < 0.01) of baseline, and GABA concentration in LHA dialysate decreased to 77 +/- 4% (P < 0.01) of baseline. The changes in dialysate GABA concentrations occurred concurrently with the animals eating and returned to baseline by 60 min. When animals were denied access to food after 2-DG, the decrease in LHA GABA was not apparent and VMH GABA remained approximately 15% above baseline at the end of the sample period. The results of the present study provide evidence that GABAergic systems in the ventral hypothalamus are responsive to alterations in glucose status.


MicroRNA ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 224-231
Author(s):  
Amin Derakhshanfar ◽  
Javad Moayedi ◽  
Mahjoob Vahedi ◽  
Abouzar Valizadeh

Background: Arum conophalloides (A. conophalloides) is a wild edible delicate plant, widely used in traditional medicine. Objective: This study aimed to examine the effects of A. conophalloides extracts on biochemical, molecular, and histopathological changes in the rat. Methods: Fifty adult male Sprague-Dawley rats were divided into 5 groups (10 each) as follows: G1 or control, received distilled water; G2 and G3, treated with the aqueous extract at doses of 200 and 400 mg/kg; G4 and G5, treated with the hydroalcoholic extract at doses of 200 and 400 mg/kg. Prior to and at the end of the experiments, the serum levels of biochemistry parameters and the relative expression of miR-122 were assessed. Moreover, the liver and kidney tissues were examined microscopically. Results: Liver and kidney tissues showed normal structure in all groups. There were no significant changes in biochemical indices or the expression of miR-122 in the extract-treated groups at the dose of 200 mg/kg. However, the group that received the aqueous extract at the dose of 400 mg/kg exhibited a significantly lower level of HDL, LDL, ALT, and ALP in comparison to the control. Additionally, miR-122 expression in this group exhibited a 10-fold increase (P=0.009). Conclusion: The serum level of hepatocyte-specific miR-122 will be more helpful in detecting hepatic changes in early stages than ALT and AST activity or histopathological evaluations of liver sections. Our findings highlight the potential hepatotoxicity of A. conophalloides aqueous extract in a rat model.


2000 ◽  
Vol 88 (6) ◽  
pp. 2023-2030 ◽  
Author(s):  
S. A. Shore ◽  
J. H. Abraham ◽  
I. N. Schwartzman ◽  
G. G. Krishna Murthy ◽  
J. D. Laporte

During ozone (O3) exposure, adult rats decrease their minute ventilation (V˙e). To determine whether such changes are also observed in immature animals, Sprague-Dawley rats, aged 2, 4, 6, 8, or 12 wk, were exposed to O3(2 ppm) in nose-only-exposure plethysmographs. BaselineV˙e normalized for body weight decreased with age from 2.1 ± 0.1 ml ⋅ min−1⋅ g−1in 2-wk-old rats to 0.72 ± 0.03 ml ⋅ min−1⋅ g−1in 12-wk-old rats, consistent with the higher metabolic rates of younger animals. In adult (8- and 12-wk-old) rats, O3caused 40–50% decreases in V˙e that occurred primarily as the result of a decrease in tidal volume. In 6-wk-old rats, O3-induced changes inV˙e were significantly less, and in 2- and 4-wk-old rats, no significant changes inV˙e were observed during O3exposure. The increased baseline V˙e and the smaller decrements in V˙e induced by O3in the immature rats imply that their delivered dose of O3is much higher than in adult rats. To determine whether these differences in O3dose influence the extent of injury, we measured bronchoalveolar lavage protein concentrations. The magnitude of the changes in bronchoalveolar lavage induced by O3was significantly greater in 2- than in 8-wk-old rats (267 ± 47 vs. 165 ± 22%, respectively, P < 0.05). O3exposure also caused a significant increase in PGE2in 2-wk-old but not in adult rats. The results indicate that the ventilatory response to O3is absent in 2-wk-old rats and that lack of this response, in conjunction with a greater specific ventilation, leads to greater lung injury.


Sign in / Sign up

Export Citation Format

Share Document