scholarly journals Effects of Large Doses of Androgen on Rodent Erythropoiesis and Body Composition

Blood ◽  
1965 ◽  
Vol 26 (4) ◽  
pp. 411-420 ◽  
Author(s):  
DAVID G. NATHAN ◽  
FRANK H. GARDNER ◽  
Alvera L. Kan

Abstract Six weeks treatment of male and female mature Sprague-Dawley rats with 8 mg. testosterone enanthate per week produced varied effects depending upon the sex of the animal. Compared to controls, the androgen-treated female rats exhibited a greater gain in body weight which was predominantly water. There was concomitant renal hypertrophy and fat loss. An accelerated rate of erythropoiesis produced a gain in total red cell volume out of proportion to the accretion of lean tissue. Treated male rats gained somewhat less water and lean tissue and much less fat than controls. Definite evidence of acceleration of erythropoiesis was not observed. It is concluded that the female rat is more sensitive to the erythropoietic effects of large doses of androgen than is the male. The erythropoietic response to androgen in the female rat appears to be independent of the effects of the hormone on body composition.

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.


2020 ◽  
Vol 318 (2) ◽  
pp. R418-R427 ◽  
Author(s):  
Reham H. Soliman ◽  
Jermaine G. Johnston ◽  
Eman Y. Gohar ◽  
Crystal M. Taylor ◽  
David M. Pollock

Genes for the epithelial sodium channel (ENaC) subunits are expressed in a circadian manner, but whether this results in time-of-day differences in activity is not known. Recent data show that protein expression of ENaC subunits is higher in kidneys from female rats, yet females are more efficient in excreting an acute salt load. Thus, our in vivo study determined whether there is a time-of-day difference as well as a sex difference in the response to ENaC inhibition by benzamil. Our results showed that the natriuretic and diuretic responses to a single dose of benzamil were significantly greater in male compared with female rats whether given at the beginning of the inactive period [Zeitgeber time 0 (ZT0), 7 AM] or active period (ZT12, 7 PM). However, the response to benzamil was not significantly different between ZT0 and ZT12 dosing in either male or female rats. There was no difference in renal cortical α-ENaC protein abundance between ZT0 and ZT12 or males and females. Given previous reports of flow-induced stimulation of endothelin-1 (ET-1) production and sex differences in the renal endothelin system, we measured urinary ET-1 excretion to assess the effects of increased urine flow on intrarenal ET-1. ET-1 excretion was significantly increased following benzamil administration in both sexes, but this increase was significantly greater in females. These results support the hypothesis that ENaC activity is less prominent in maintaining Na+ balance in females independent of renal ET-1. Because ENaC subunit genes and protein expression vary by time of day and are greater in female rat kidneys, this suggests a clear disconnect between ENaC expression and channel activity.


1991 ◽  
Vol 260 (2) ◽  
pp. H453-H458 ◽  
Author(s):  
J. N. Stallone ◽  
J. T. Crofton ◽  
L. Share

Previously, we reported that, in the rat, pressor responsiveness to vasopressin (VP) is higher in males than in females during most phases of the estrous cycle. To explore the role of the vasculature in this phenomenon, we examined vascular reactivity to VP in thoracic aortas of male rats and female rats during each phase of the estrous cycle. Aortic rings were prepared from age-matched male and female Sprague-Dawley rats and mounted for isometric tension recording. Maximal response of female aortas to VP (4,246 +/- 163 mg/mg ring dry wt) was more than twice (P less than 0.001) that of male aortas (1,877 +/- 215 mg/mg ring wt). Sensitivity of female aortas to VP was substantially higher (P less than 0.001) than that of male aortas (EC50: 10.9 +/- 0.7 vs. 19.0 +/- 1.6 nM, respectively). Maximal rate of tension development (dT/dtmax) during contraction with VP was nearly twofold higher (P less than 0.01) in female aortas (536 +/- 23 mg/min) than in male aortas (300 +/- 19 mg/min). Maximal response, sensitivity, and dT/dtmax of female aortas did not vary significantly during the estrous cycle. Maximal response of female aortas to phenylephrine (PE; 1,251 +/- 93 mg/mg ring wt) was half that (P less than 0.001) of male aortas (2,546 +/- 194 mg/mg ring wt); sensitivity to PE did not differ significantly (EC50: 0.33 +/- 0.02 vs. 0.38 +/- 0.06 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


1985 ◽  
Vol 54 (3) ◽  
pp. 593-603 ◽  
Author(s):  
Eisa Omer Ahmed ◽  
Yudkin John

1. The claims that rats fed on diets with ‘brown sugar’ (unrefined muscovado) perform better in a number of ways than do rats fed on refined white sugar (sucrose) have been examined.2. Male Wistar rats were fed on purified diets from weaning, in which the carbohydrate component was either maize starch or unrefined sugar or sucrose. The sugars produced no differences in growth rate, body composition, or the weights of liver or kidneys. Compared with sucrose, unrefined sugar produced an increase in blood cholesterol and in the activity of hepatic fatty acid synthetase, and a greater increase in blood triglyceride. In confirmation of earlier results, rats fed on either sugar had heavier livers and kidneys, increased activity of hepatic glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and a higher concentration of plasma triglyceride compared with rats fed on maize starch.3. Female Sprague-Dawley rats were fed on the same three diets as the male rats, and mated when they weighed about 200 g. No difference was seen in their ability to mate, the progress of pregnancies, or the sizes of the litters. Does fed on unrefined sugar produced litters of higher viability than did does fed on starch or sucrose. Survival was between 85 and 100% with unrefined sugar and between 30 and 75% with starch or sucrose.4. Unrefined muscovado sugar has thus been shown to contain a factor required by female rats for the proper viability of their pups. This may be the same ‘Reproductive Factor R’ as that described by Wiesner & Yudkin (1951). In certain circumstances, unrefined muscovado sugar might therefore contribute to the nutritional value of a human diet, although in what circumstances, in what respect and to what extent it might do so, is by no means clear.


Author(s):  
Sylvia E West ◽  
Jonathan C Lee ◽  
Tinika N Johns ◽  
Elizabeth A Nunamaker

Due to their unpredictability and variable effects, injectable anesthetic regimens in laboratory rodent species warrant refinement. In our study we sought to evaluate alfaxalone, which has gained recent popularity in veterinary medicine, alone and in combination with dexmedetomidine to evaluate their anesthetic ability in Sprague–Dawley rats when administered intraperitoneally. Three doses of alfaxalone only and 4 dose combinations of alfaxalone-dexmedetomidine were tested in males and female rats. The time to induction, anesthetic duration, pulse rate, respiratory rate, temperature, and time to recovery were recorded by a blind observer. The level of anesthesia induced by the various anesthetic protocols was assessed by using pedal withdrawal reflex to a noxious stimulus and scored according to the response. Dependent on the treatment group, atipamezole or saline was administered intraperitoneally once animals reached 60 min of anesthesia. Regardless of the dose, alfaxalone alone achieved only a sedative level of anesthesia, whereas all alfaxalone-dexmedetomidine combinations led to a surgical level of anesthesia in all animals. Anesthesia regimens using alfaxalone alone and in combination with dexmedetomidine demonstrated sex-associated differences, with female rats maintaining longer durations of sedation or anesthesia than their male counterparts. Both male and female rats displayed decreases in physiologic parameters consistent with the effects of dexmedetomidine. Given the results described herein, we recommend 20 mg/kg alfaxalone for sedation and 30 mg/kg alfaxalone combined with 0.05 mg/kg dexmedetomidine for surgical anesthesia in female rats. Appropriate doses of alfaxalone only and alfaxalone-dexmedetomidine for male rats were not determined in this study and need further evaluation.


2020 ◽  
Vol 10 (5) ◽  
pp. 270 ◽  
Author(s):  
Samuel J. Hogarth ◽  
Elvan Djouma ◽  
Maarten van den Buuse

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Brandon A Kemp ◽  
Nancy L Howell ◽  
Robert M Carey

Endogenous renal des-aspartyl 1 -angiotensin II (angiotensin III) activates renal proximal tubule AT 2 receptors (AT 2 Rs) and induces natriuresis via a nitric oxide-cyclic GMP signaling pathway. The present study explores the ability of highly selective non-peptide AT 2 R agonist Compound 21 (C21) to induce natriuresis. Sprague-Dawley rats (12 weeks old; male N=22; female N=18) were studied in the presence and absence of concurrent 24-h AT 1 R blockade with candesartan (CAND;0.01 mg/kg/min). Rats were anesthetized with Inactin 100 mg/kg i.p., uninephrectomized and instrumented for delivery of 3 cumulative 30-min i.v. infusions of C21 (100, 200, and 300 ng/kg/min) following a 30-min control infusion of vehicle. Mean arterial pressure (MAP) was measured for all periods and urine Na + excretion rate (U Na V) was calculated for the control and final C21 collection periods. To determine whether the systemically induced natriuresis is mediated by renal AT 2 Rs, PD-123319 (PD), a specific AT 2 R antagonist, was infused directly into the renal cortical interstitium(20 μg/kg/min and 10 μg/kg/min for females and males, respectively) during the i.v. C21 infusions. In female rats, C21 increased U Na V from 1.5 ± 0.20 to 7.48 ± 0.95 μmol/min (P<0.0001). This response was abrogated by concurrent intrarenal PD infusion [control 0.74 ± 0.19 vs. C21 2.02 ± 0.50 μmol/min (P<0.001from C21 alone). Systemic CAND administration augmented the natriuretic response to C21 [control 1.29 ± 0.25 vs. C21 10.68 ± 0.70 μmol/min (P<0.05 from C21 alone)]. In male rats, C21 increased U Na V from 0.46 ±0.08 to 6.21 ± 1.33 μmol/min (P<0.01). This response was blocked by concurrent intrarenal PD infusion [control 0.39 ± 0.11 vs. C21 1.69 ± 0.53 μmol/min (P<0.05 from C21 alone). Systemic CAND did not significantly alter the natriuretic response to C21 alone [control 0.49 ± 0.15 vs. C21 7.67 ± 0.72 μmol/min (P = NS from C21 alone). In female rats, CAND augmented the natriuretic response to C21 over that of male rats (P<0.01). Systemic arterial pressures were decreased by CAND in both male and female rats but were unchanged by C21 alone or together with intrarenal PD. C21 induces natriuresis via renal AT 2 R activation in both male and female rats. These data suggest the potential for AT 2 R agonist therapy in hypertension.


2020 ◽  
Vol 39 (8) ◽  
pp. 1079-1094 ◽  
Author(s):  
H Rehman ◽  
S Jahan ◽  
I Ullah ◽  
P-O Thörnqvist ◽  
M Jabbar ◽  
...  

The present study investigated the reproductive toxicity of furan in an Extended One-Generation Reproductive Toxicity Study in rats. Sprague Dawley F0 weaning rats (30 per sex per group) were exposed to furan orally at 0, 1, 2.5, 5, and 10 mg kg−1 for 10 weeks (males) and 2 weeks (females) and then mated. Results of F0 indicated that in the furan-treated groups (5 mg kg−1 and 10 mg kg−1), body weight (bw) gain decreased during prebreed and gestational period while increased during lactation periods. F0 animals prebreeding exposure resulted in head tilt and foot splay at 10 mg kg−1. Number of live pups at birth were decreased ( p < 0.001) at 10 mg kg−1. At postnatal day (PND) 70, a significant ( p = 0.03) decrease in testosterone levels of male rats and estrogen levels of female rats ( p = 0.05) was observed in 10 mg kg−1 furan-treated group in F1 generation. Luteinizing hormone, follicle-stimulating hormone, and progesterone levels were also reduced, but their reduction was not statistically significant in all groups. In higher dose furan group (10 mg kg−1), testicular and ovarian weights were reduced in F1 generation at PND 70, with decreased daily sperm production ( p = 0.01) and disturbed estrous cyclicity ( p < 0.01). Some histopathological changes were also observed in testis and ovaries in groups whose parents were previously exposed to 10 mg kg−1 bw of furan group. Based on the above results, it is suggested that exposure to food-based contaminant furan induced remarkable changes in the F0 (parental stage) and F1 (offspring, pubertal, and adult stage) generations of Sprague Dawley rats.


1992 ◽  
Vol 29 (2) ◽  
pp. 145-151 ◽  
Author(s):  
D. E. Gunson ◽  
P. S. Sahota ◽  
W. O. Iverson ◽  
R. Y. Chau ◽  
G. M. McCormick ◽  
...  

Male and female Sprague-Dawley rats were given CGS 21595, a pro-drug that is almost immediately metabolized to CGS 19213, a naphthoquinone that acts as a 5-lipoxygenase inhibitor. The compound was administered by gavage to five groups of Sprague-Dawley rats (group Nos. 1, 5, n = 30; group Nos. 2–4, n = 20) at daily doses of 0, 50, 150, 500, or 1,000 mg/kg for 13 weeks. Rats in the higher dose groups had a reduced weight gain, but significant neurologic signs were not observed. A peripheral neuropathy consisting predominantly of myelin destruction in the spinal nerve roots and sciatic nerves was seen in male rats treated with ≥ 150 mg/kg CGS 21595 and in female rats treated with ≥50 mg/kg CGS 21595 for 13 weeks. This lesion was not fully reversible after a recovery period of 4 weeks. Lesions consisted of ballooning of myelin sheaths, infiltration by macrophages, demyelination, and occasional areas of remyelination. Axons were generally preserved, and the brain and spinal cord were not affected. Male and female rats in all treatment groups had cytoplasmic hyaline droplets in the proximal renal tubules. This change was reversible after 4 weeks and was not associated with any other adverse effects on the kidney.


2001 ◽  
Vol 20 (5) ◽  
pp. 269-274 ◽  
Author(s):  
Ralph I. Freudenthal ◽  
David Brandwene ◽  
Welmoed Clous

Phosflex 51B is a flame retardant plasticizer that is blended with polyvinyl chloride films to effectively control product flammability. Its composition places it in the butylated triphenyl phosphate category. Previous studies have shown Phosflex 51B to have low acute toxicity, to lack teratogenic and mutagenic activity, and to not induce delayed peripheral neuropathy. The present study was conducted to determine the toxicity of Phosflex 51B after repeated dietary exposure. Four groups, each consisting of 20 male and 20 female Sprague-Dawley rats, received rodent diet containing either 0, 100, 400, or 1600 ppm for 90 days. Parameters measured include body weight, food consumption, clinical observations, hematology, clinical chemistry, and cholinesterase activity. Tissues were examined at necropsy for gross changes and were processed for microscopic pathology. There were no significant treatment-related effects on body weights, food consumption, hematology and clinical chemistry, or cholinesterase values. A significant increase was observed in the absolute and relative mean weights of livers in high-dose male rats, the mean relative fiver weights of the high-dose female animals, the mean relative kidney weights of the high-dose male rats, and the mean absolute weights of the adrenal glands from high-dose female rats. Neither gross nor microscopic pathology examinations revealed tissue changes in these organs or in any other organs. Although increases in fiver, kidney, and adrenal weights were observed in certain animals in the 1600-ppm high-dose group, the administration of Phosflex 51B did not result in significant treatment-related adverse effects at dietary dose levels of 100 and 400 ppm. The no-observable-effect level (NOEL) in this study is 400 ppm.


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