Influence of sex and inducer treatment on the high- and low-affinity forms of hepatic microsomal erythromycin N-demethylase in rats

1990 ◽  
Vol 68 (12) ◽  
pp. 1510-1513 ◽  
Author(s):  
Tom Chang ◽  
Marc Levine ◽  
Gail D. Bellward
Keyword(s):  
Tween 80 ◽  
Female Rats ◽  
Male Rats ◽  
Mixed Function Oxidase ◽  
Adult Rats ◽  
Once Daily ◽  
Relative Contribution ◽  
Fitting Procedure ◽  
Hepatic Microsomes ◽  
Mixed Function Oxidase Activity

To study the regulation of the multiple forms of erythromycin N-demethylase, we determined the influence of sex and inducer treatment on this mixed-function oxidase activity in adult Wistar rats injected intraperitoneally once daily for 4 days with dexamethasone, pregnenolone-16α-carbonitrile, phenobarbital, or 2% Tween 80 (control). Based on the results from a computer curve-fitting procedure (ENZFITTER) as well as Eadie–Hofstee and Lineweaver–Burk plots, at least two forms of erythromycin N-demethylase were present in control, dexamethasone, pregnenolone-16α-carbonitrile, and phenobarbital-treated male rats and in control and dexamethasone-treated female rats. Only a high-affinity form was apparent in pregneno-lone-16α-carbonitrile and phenobarbital-treated female rats. Therefore, more than one form of erythromycin N-demethylase exists in hepatic microsomes from adult rats, depending on sex and inducer treatment. As well, at a substrate concentration commonly used in the erythromycin N-demethylase assay, the relative contribution of the high- and low-affinity forms to the enzyme activity varies with sex and inducer treatment.Key words: erythromycin N-demethylase, dexamethasone, pregnenolone-16α-carbonitrile, phenobarbital, mixed-function oxidase.

INDUCTION OF GOITRE BY PTU OR KClO4 IN MALE AND FEMALE RATS. EFFECT OF GONADECTOMY

1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia
Keyword(s):  
Iodine Content ◽  
High Plasma ◽  
Disc Electrophoresis ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Male And Female ◽  
Glucose Levels ◽  
Male And Female Rats ◽  
Tsh Levels

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.

FACTORS INFLUENCING THE EXCRETION OF A FAT-MOBILIZING SUBSTANCE IN THE URINE OF RATS

1966 ◽  
Vol 44 (1) ◽  
pp. 95-101 ◽  
Author(s):  
J. R. Beaton ◽  
A. J. Szlavko ◽  
J. A. F. Stevenson
Keyword(s):  
Body Weight ◽  
Sex Difference ◽  
Specific Activity ◽  
Young Male ◽  
Total Activity ◽  
Female Rats ◽  
Male Rats ◽  
Diabetic Rat ◽  
Adult Rats ◽  
Factors Influencing

The effect of various factors on excretion of a lipid-mobilizing activity in FMS IA (anorexigenic) and in FMS IB (fat-mobilizing) by the fasting rat has been investigated. During fasting, the greatest excretion of such activity in FMS IA and FMS IB occurred in the first 24 hours and diminished thereafter up to 72 hours; and the specific activity of FMS IB was greatest in the first 24 hours whereas that of FMS IA was constant throughout. The hypothalamicobese rat excretes FMS IA and FMS IB in greater than normal amounts. The alloxan-diabetic rat excretes less total activity of FMS IA and IB than do control animals. Young male rats excrete greater amounts of FMS IB, but not of FMS IA, than do adult rats, the greatest excretion per 100 g body weight being observed at approximately 37 days of age. At 27 days of age (prepuberty), male rats excreted a greater total activity of FMS IB but not of FMS IA than did female rats. At 90 days of age (post-puberty), there was no apparent sex difference in the amount of total activity of FMS IB excreted per rat, but when expressed per 100 g body weight, females excreted more FMS IB than did males.

EFFECTS OF TESTOSTERONE MEDIATED OR MODULATED BY PITUITARY FACTORS

1975 ◽  
Vol 67 (1) ◽  
pp. 71-79 ◽  
Author(s):  
P. DE MOOR ◽  
M. ADAM-HEYLEN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN
Keyword(s):  
Body Weight ◽  
Testosterone Propionate ◽  
Total Body Weight ◽  
Seminal Vesicles ◽  
Female Rats ◽  
Male Rats ◽  
Intact Male ◽  
Adult Rats ◽  
Organ Weights ◽  
Total Body

SUMMARY Adult rats of both sexes were either gonadectomized or hypophysectomized and gonadectomized. Three to eight weeks later they were treated for 14 consecutive days with oil or with 75 or 200 μg testosterone propionate (TP) per 100 g body weight. The animals were killed and for each sex the gonadectomized animals were compared with the hypophysectomized-gonadectomized animals as far as their NADPH- and NADH-dependent 3α-hydroxysteroid dehydrogenases (3α-HSD) in renal microsomes, transcortin levels in serum and five organ weights relative to total body weight were concerned. For two of the latter, i.e. the relative kidney and prostatic weights, no significant differences were found. Transcortin levels, relative adrenal weights and renal NADPH-dependent 3α-HSD activities were higher in oil-treated gonadectomized animals than in oil-treated hypophysectomized-gonadectomized animals. The opposite was found for the relative weights of uterus and seminal vesicles and renal NADH-dependent 3α-HSD activities. These differences between gonadectomized and hypophysectomized-gonadectomized animals disappeared after TP treatment as far as transcortin levels were concerned but remained for the five other parameters. After gonadectomy sexual differences subsisted for all parameters studied. But whereas intact male rats had higher NADH-dependent 3α-HSD activities than female rats the opposite was found after gonadectomy. After gonadectomy plus hypophysectomy the between sex differences disappeared as far as transcortin levels were concerned but remained in the other parameters studied.

Effect of dexamethasone treatment on the biotransformation of glyceryl trinitrate: cytochrome P450 3A1 mediated activation of rat aortic guanylyl cyclase by glyceryl trinitrate

1994 ◽  
Vol 72 (12) ◽  
pp. 1513-1520 ◽  
Author(s):  
Bernard J. McDonald ◽  
Greg J. Monkewich ◽  
Patrick G. Long ◽  
Diane J. Anderson ◽  
Paul E. Thomas ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Glyceryl Trinitrate ◽  
Guanylyl Cyclase ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Treated Male ◽  
Cyclase Activation ◽  
Male And Female Rats ◽  
Hepatic Microsomes

It is generally accepted that organic nitrates act via vascular biotransformation to an activator of guanylyl cyclase (presumably NO), resulting in increased cyclic GMP accumulation and vascular smooth muscle relaxation. Previously, we have shown that cytochrome P450 can mediate the biotransformation of glyceryl trinitrate (GTN) and that at least a portion of this biotransformation results in the formation of an activator of guanylyl cyclase. To assess the role of the cytochrome P450 3A subfamily in this phenomenon, we treated male and female rats with dexamethasone (DEX) (150 mg/kg, i.p., daily for 3 days). Under anerobic conditions, hepatic microsomal biotransformation of GTN was increased three-fold in DEX-treated male rats compared with all other treatment groups. Incubation of aortic 100 000 × g supernatant fraction from untreated rats (as a source of guanylyl cyclase) with GTN and hepatic microsomes from all groups resulted in concentration-dependent increases in guanylyl cyclase activation. Microsomes from DEX-treated male and female rats demonstrated a significantly greater activation of guanylyl cyclase compared with microsomes from untreated males and females. Furthermore, GTN-induced guanylyl cyclase activation mediated by microsomes from DEX-treated male and female rats was markedly inhibited by a polyclonal antibody raised to rat CYP3A1. Since CYP3A2 is absent or very low in hepatic microsomes from DEX-treated adult female rats, this identifies CYP3A1 as an isoform capable of biotransforming GTN to an activator of guanylyl cyclase. Similarly, CYP2C11 was identified as an isoform capable of biotransforming GTN to an activator of guanylyl cyclase, since monoclonal antibody to CYP2C11 inhibited GTN-induced activation of guanylyl cyclase mediated by microsomes from control male rats. In both male and female rats, DEX treatment had no effect on GTN-induced relaxation of isolated aorta. However, biotransformation of GTN in intact aorta from DEX-treated male rats was decreased. This suggests that DEX treatment affects only the aortic biotransformation of GTN that is not involved in the formation of an activator of guanylyl cyclase.Key words: glyceryl trinitrate, dexamethasone, guanylyl cyclase, cytochrome P450, vasodilation, biotransformation.

scholarly journals MICROBODIES IN EXPERIMENTALLY ALTERED CELLS

1969 ◽  
Vol 40 (3) ◽  
pp. 734-746 ◽  
Author(s):  
Donald Svoboda ◽  
Daniel Azarnoff ◽  
Janardan Reddy
Keyword(s):  
Catalase Activity ◽  
Estradiol Benzoate ◽  
Significant Degree ◽  
Female Rats ◽  
Male Rats ◽  
Rapid Decline ◽  
Hypolipidemic Effect ◽  
Intact Male ◽  
Adult Rats ◽  
Sufficient Cause

The liver cells of intact male rats given ethyl-α-p-chlorophenoxyisobutyrate (CPIB) characteristically show a marked increase in microbodies and in catalase activity, while those of intact female rats do not. In castrated males given estradiol benzoate and CPIB the increase in catalase activity and microbody proliferation is abolished, while in castrated females given testosterone propionate and CPIB the livers show a marked increase in microbodies and in catalase activity. No sex difference in microbody and catalase response is apparent in fetal and neonatal rats. Both sexes show a sharp rise in catalase activity on the day of birth, with a rapid decline at 5 days after birth. Thyroidectomy abolishes the hypolipidemic effect of CPIB in rats, but microbody proliferation and increase in catalase activity persists in thyroidectomized male rats, indicating that microbody proliferation can be independent of hypolipidemia. Adrenalectomy does not alter appreciably the microbody-catalase response to CPIB. These experiments demonstrate that (1) in adult rats, hepatic microbody proliferation is dependent to a significant degree upon male sex hormone but is largely independent of thyroid or adrenal gland hormones; (2) hepatic microbody proliferation is independent of the hypolipidemic effect of CPIB; (3) displacement of thyroxine from serum protein may not be sufficient cause for stimulation of microbody formation.

scholarly journals The Effect of Gender on Brain Tissue Changes Induced by Renal Ischemia-Reperfusion Injury in Adult Rats

2019 ◽  
Vol 8 (2) ◽  
pp. 113-118
Author(s):  
Fakhri Armin ◽  
Fariba Azarkish ◽  
Ali Atash Ab Parvar ◽  
Aghdas Dehghani
Keyword(s):  
Brain Tissue ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Left Kidney ◽  
Renal Ischemia ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Sensitive Organ ◽  
The Brain

Background: Renal ischemia-reperfusion (RIR) is a common clinical injury that affects the function of other remote organs such as the brain by initiating a cascade of complex and wide-ranging inflammatory responses. RIR also follows a different course in men and women. Since there is little information on the effect of RIR on the brain as a sensitive organ in both males and females, the present research was performed to investigate the effect of gender on RIR-induced brain tissue alterations in adult rats. Materials and Methods: In this study, 28 Wistar rats (14 female and 14 male rats) weighing 200 ± 20 g were divided into the following groups: 1- male sham (MS), 2- female sham (FS), 3- male ischemia (MI) with 3-hour reperfusion (ISC3hr), and 4- Female ischemia (FI) with 3-hour reperfusion (ISC3hr). Bilateral renal ischemia was induced for 45 minutes and blood samples were taken after reperfusion for the measurements of serum blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitrite levels. The left kidney was removed for evaluation of MDA and tissue nitrite levels. Right kidney and brain tissue underwent histological examination. Results: Serum BUN level increased in both genders. Serum nitrite level was significantly different between both genders, meaning that it was increased in the female rats as compared to male ones. Overall brain tissue damage was significantly increased in males compared to females. Conclusion: RIR has an effect on the function and tissue of kidney and brain in both genders. Female rats are more susceptible to the nitric oxide system than the male ones. This study showed that male brain tissue was more susceptible to RIR. Therefore, gender is one of the important factors that should be considered in clinical treatments.

scholarly journals Gender Differences in the Effect of Prenatal Methamphetamine Exposure and Challenge Dose of Other Drugs on Behavior of Adult Rats

2013 ◽  
pp. S99-S108 ◽  
Author(s):  
R. ŠLAMBEROVÁ ◽  
E. MACÚCHOVÁ ◽  
K. NOHEJLOVÁ-DEYKUN ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Adult Male ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Male Rats ◽  
Prenatally Exposed ◽  
Challenge Dose ◽  
Adult Rats ◽  
Male And Female ◽  
Male And Female Rats

The aim of the present study was to compare the response to acute application of several drugs in adult male and female rats prenatally exposed to methamphetamine (MA). Spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug [amphetamine – 5 mg/kg; cocaine – 5mg/kg; MDMA (3,4-methylenedioxymethamphetamine) – 5 mg/kg; morphine – 5 mg/kg; THC (delta9-tetrahydrocannabinol) – 2 mg/kg] or saline was injected prior to testing. Our data demonstrate that prenatal MA exposure did not affect behavior in male rats with cocaine or morphine treatment, but increased locomotion and exploration in females. Application of amphetamine and MDMA in adulthood increased activity in both sexes, while cocaine and THC only in female rats. Morphine, on the other hand, decreased the activity in the Laboras test in both sexes. As far as sex and estrous cycle is concerned, the present study shows that males were generally less active than females and also females in proestrus-estrus phase of the estrous cycle were more active than females in diestrus. In conclusion, the present study shows that the prenatal MA exposure does not induce general sensitization but affects the sensitivity to drugs dependently to mechanism of drug action and with respect to gonadal hormones.

scholarly journals Sex Difference in Plasma Deoxyribonuclease Activity in Rats

2021 ◽  
pp. 913-920
Author(s):  
Ľ Janovičová ◽  
B. Gromová ◽  
D. Drobná ◽  
B. Konečná ◽  
E. Renczés ◽  
...  
Keyword(s):  
Sex Differences ◽  
Sex Difference ◽  
Extracellular Dna ◽  
Female Rats ◽  
Male Rats ◽  
Dnase Activity ◽  
Adult Rats ◽  
Opposite Sex ◽  
Diffusion Assay ◽  
Deoxyribonuclease Activity

Extracellular DNA (ecDNA) activates immune cells and is involved in the pathogenesis of diseases associated with inflammation such as sepsis, rheumatoid arthritis or metabolic syndrome. DNA can be cleaved by deoxyribonucleases (DNases), some of which are secreted out of cells. The aim of this experiment was to describe plasma DNase activity in relation to extracellular DNA in adult rats, to analyse potential sex differences and to prove whether they are related to endogenous testosterone. Adult Lewis rats (n=28) of both sexes were included in the experiment. Male rats were gonadectomized or sham-operated and compared to intact female rats. Plasma ecDNA and DNase activity were measured using fluorometry and single radial enzyme diffusion assay, respectively. Concentrations of nuclear ecDNA and mitochondrial ecDNA were determined using real-time PCR. Females had 60% higher plasma DNase activity than males (p=0.03). Gonadectomy did not affect plasma DNase in males. Neither the concentration of total ecDNA, nor nuclear or mitochondrial DNA in plasma differed between the groups. No significant correlations between DNase and ecDNA were found. From previous studies on mice, it was expected, that male rats will have higher DNase activity. In contrast, our study in rats showed the opposite sex difference. This sex difference seems not to be caused by endogenous testosterone. Interestingly, no sex differences were observed in plasma ecDNA suggesting a complex or missing association between plasma ecDNA and DNase. The observed sex difference in plasma DNase should be taken into account in animal models of ecDNA-associated diseases.

Hyperprolactinaemia attenuates the gonadotrophin releasing hormone receptor response to gonadectomy in rats

1982 ◽  
Vol 95 (2) ◽  
pp. 267-274 ◽  
Author(s):  
R. N. Clayton ◽  
L. C. Bailey
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Serum Prolactin ◽  
Intact Male ◽  
Adult Rats ◽  
Releasing Hormone ◽  
Receptor Response ◽  
Serum Lh ◽  
Gonadotrophin Releasing Hormone ◽  
Qualitative Index

Measurement of pituitary gonadotrophin releasing hormone (Gn-RH) receptor content provides a qualitative index of prior exposure of the pituitary gland to endogenous Gn-RH. The effect of moderate hyperprolactinaemia (serum prolactin = 95–250 μg/l), achieved with three pituitary grafts beneath the renal capsule, on the pituitary Gn-RH receptor content and serum LH responses to gonadectomy of adult rats has been studied. In males the presence of hyperprolactinaemia for 7 days completely prevented the increase in Gn-RH receptor content 3 days after castration and inhibited the serum LH rise by 45%. By 6 days after castration, Gn-RH receptors had increased in the hyperprolactinaemic castrated animals but values were 33% lower than in sham-grafted controls, while the serum LH increase was attenuated by 30%. Pituitary LH content was also lower in grafted castrated animals 6 days after castration. Hyperprolactinaemia for 3 weeks had no effect on Gn-RH receptors or pituitary LH content of intact male rats, although basal serum LH was decreased by 50%. Hyperprolactinaemia also attenuated the increases in Gn-RH receptors, serum LH and pituitary LH which occurred 6 days after ovariectomy in female rats. In all experiments the pituitary content of prolactin was reduced by 80–90% in animals bearing pituitary grafts. These results suggest that hyperprolactinaemia restricts the Gn-RH receptor response to gonadectomy by decreasing endogenous hypothalamic Gn-RH secretion.

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