scholarly journals Male-specific suppression of hepatic microsomal UDP-glucuronosyl transferase activities toward sex hormones in the adult male rat administered bisphenol A

2002 ◽  
Vol 368 (3) ◽  
pp. 783-788 ◽  
Author(s):  
Noriaki SHIBATA ◽  
Junya MATSUMOTO ◽  
Ken NAKADA ◽  
Akira YUASA ◽  
Hiroshi YOKOTA

Various adverse effects of endocrine disruptors on the reproductive organs of male animals have been reported. We found that UDP-glucuronosyltransferase (UGT) activities towards bisphenol A, testosterone and oestradiol were significantly decreased in liver microsomes prepared from adult male Wistar rats administered with the endocrine disruptor bisphenol A (1mg/2 days for 2 or 4 weeks). However, suppression of the transferase activities was not observed in female rats, even after bisphenol A treatment for 4 weeks. Diethylstilbestrol, which is well known as an endocrine disruptor, had the same effects, but p-cumylphenol had no effect on UGT activities towards sex hormones. Co-administration of an anti-oestrogen, tamoxifen, inhibited the suppression of the transferase activities by bisphenol A. Western blotting analysis showed that the amount of UGT2B1, an isoform of UGT which glucuronidates bisphenol A, was decreased in the rat liver microsomes by the treatment. Northern blotting analysis also indicated that UGT2B1 mRNA in the liver was decreased by bisphenol A treatment. The suppression of UGT activities, UGT2B1 protein and UGT2B1 mRNA expression did not occur in female rats. The results indicate that bisphenol A treatment reduces the mRNA expression of UGT2B1 and other UGT isoforms that mediate the glucuronidation of sex hormones in adult male rats, and this suggests that the endocrine balance may be disrupted by suppression of glucuronidation.

1988 ◽  
Vol 251 (2) ◽  
pp. 475-481 ◽  
Author(s):  
K Saarem ◽  
J I Pedersen

In a previous study we found that liver mitochondrial side-chain hydroxylation of vitamin D3 (cholecalciferol) and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was higher in female than in male rats [Saarem & Pedersen (1987) Biochem. J. 247, 73-78]. The present paper describes the effects of age, gonadectomy and hypophysectomy on these activities. The sex difference became manifest above the age of 7 weeks. Ovariectomy and/or injection of oestradiol valerate had no effect on the hydroxylase activities in adult females. Castration increased, and subsequent testosterone treatment decreased, the hydroxylase activities in adult males. Hypophysectomy had no effect in females, but increased the hydroxylase activities in males. Testosterone treatment had no effect in hypophysectomized females or males. Injection of oestradiol valerate had no effect on the hydroxylase activities in hypophysectomized females. In hypophysectomized males this treatment had no effect on the vitamin D3 25-hydroxylase activity, but decreased the C27-steroid 27-hydroxylase activity in males. Microsomal 1 alpha-hydroxyvitamin D3 25-hydroxylase activity was lower in females than in males in all age groups. Castration or hypophysectomy decreased the activity in male rats. It is concluded that, in adult female rats, the mitochondrial side-chain hydroxylation of vitamin D3 and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol is independent of sex hormones. In males these activities are regulated by influence of sex hormones on the hypophysis, probably by the presence of androgens in the neonatal period. Different effects on the two hydroxylases indicate the presence of at least two different cytochromes P-450 in rat liver mitochondria.


1987 ◽  
Vol 247 (1) ◽  
pp. 73-78 ◽  
Author(s):  
K Saarem ◽  
J I Pedersen

The effect of sex hormones on hydroxylation of cholecalciferol (‘vitamin D3’) and of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol has been investigated in female- and male-rat livers. The mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities were respectively 4.6- and 2.7-fold higher in female- than in male-rat livers. The microsomal 1 alpha-hydroxycholecalciferol 25-hydroxylase was 2.8-fold higher in male- than in female-rat liver. No significant difference was found in the microsomal 25-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. Liver microsomes (microsomal fractions) from male, but not from female, rats also catalysed 1-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. Injection of testosterone into female rats decreased the mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities, but not to a statistically significant extent. Testosterone treatment had no effect on the microsomal hydroxylases in female-rat liver. Injection of oestradiol valerate to male rats resulted in increased activities of both mitochondrial hydroxylases to the same levels as those of control females, while the microsomal enzyme activities decreased. The present results indicate that sex hormones exert a regulatory control on the mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities.


2019 ◽  
pp. S339-S346
Author(s):  
L. MIHALČÍKOVÁ ◽  
A. OCHOZKOVÁ ◽  
R. ŠLAMBEROVÁ

Drug addiction and its consequences on social life and behavior is currently a worldwide problem. Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic. MA elevates mood, increases concentration, reduces appetite, and promotes weight loss. However, high doses and long-term abuse can induce psychosis, hallucinations, paranoia, violent behavior, and can lead to cardiovascular problems. Regarding its high prevalence and negative impact on health and social life, MA needs to be fully investigated. Previous studies have demonstrated the impairing effect of MA drug abuse on female behavior. However, MA’s influence on male sexual behavior is not entirely clear. The aim of this study was to examine the effect of MA exposure on sexual behavior and spontaneous locomotor activity of adult male rats. MA was administrated subcutaneously at a dose of 5 mg/kg daily for a period of 30 days. The control group was exposed to saline (SA) at the same time and same volume. At the end of the application period, exposed male rats were paired with non-treated female rats, and their behavior was recorded for 2 h. Sexual mating behavior was described in terms of mounting frequency, intromission frequency, ejaculation frequency, sniffing time, intromission latency and the post-ejaculatory interval. Spontaneous locomotor activity in postnatally exposed male rats was studied using the Laboras apparatus. Acute doses of MA (1 mg/kg) or SA were administrated to probe the sensitizing effect of previous chronic MA exposure. Afterward, the animal was placed in an unknown environment and monitored for 1 h. Behavior was automatically evaluated using Laboras software by analyzing the following parameters: duration of locomotion (s), duration of immobility (s), rearing (vertical exploratory behavior), time spent grooming (s), average speed (mm/s), and distance traveled (m). Our results indicate that MA administration has a negligible effect on the sexual behavior of adult male rats. However, more experiments have to be performed to examine the influence of MA exposure on spermatogenesis and the behavior of offspring. Data from the Laboras test showed that MA exposure has a significant effect on locomotor activity in both acute as well as subchronic MA application. In conclusion, our results show that administration of MA in adult male rats does not affect sexual performance and motivation but does increase locomotor and exploratory activity in an unknown environment.


1976 ◽  
Vol 81 (1) ◽  
pp. 198-207 ◽  
Author(s):  
H. L. Verjans ◽  
K. B. Eik-Nes

ABSTRACT Effect of intramuscular administration of ACTH or dexamethasone on blood serum levels of testosterone, LH and FSH was examined in intact and castrated, adult, male rats. Six IU ACTH or 1 mg dexamethasone were given daily for 7 days. Corticotrophin treatment had no influence on circulating testosterone, LH and FSH in intact or castrated male rats. Dexamethasone administration resulted in a slight elevation of serum FSH in intact animals but not in castrates. LH and testosterone remained normal in both intact and castrated animals injected with dexamethasone. Under our conditions of study the secretions from the adrenal gland appear to be insignificant for the regulation of pituitary secretion of gonadotrophins in the male rat.


1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.


Author(s):  
Devangam Sheshadri Shekar

Object: The present investigation has been carried out to find out the effect of yohimbine on clomipramine-induced sexual dysfunction in male rats.Methods: The male rats were treated with clomipramine and yohimbine simultaneously for 60 days. During the treatment, all the male rats werechallenged with the female rats which are in estrous phase and their sexual behavior was observed under dim red light. Half of the animals in each group and remaining on 60 day were sacrificed, blood was collected and serum separated. Testis was collected and preserved in 10% formalin forsubsequent histopathological examination. thResults: The study reveals that yohimbine failed to antagonize the clomipramine-induced sexual dysfunction in male rats in all aspects, except thepartial improvement in the sexual behavior.Conclusion: Yohimbine a well-known aphrodisiac failed to antagonize the clomipramine-induced sexual dysfunction in male rats. The decrease intestosterone levels, a decrease in spermatozoa count were continued even in the presence of yohimbine except improvement in the sexual behaviorparameters. Hence, yohimbine could not be a safe antidote against clomipramine-induced sexual dysfunction in male rats.Keywords: Yohimbine, Clomipramine, Testosterone, Male rat sexual competence, Testicular damage.


2018 ◽  
Vol 314 (1) ◽  
pp. R12-R21 ◽  
Author(s):  
Hershel Raff ◽  
Brian Hoeynck ◽  
Mack Jablonski ◽  
Cole Leonovicz ◽  
Jonathan M. Phillips ◽  
...  

Care of premature infants often requires parental and caregiver separation, particularly during hypoxic and hypothermic episodes. We have established a neonatal rat model of human prematurity involving maternal-neonatal separation and hypoxia with spontaneous hypothermia prevented by external heat. Adults previously exposed to these neonatal stressors show a sex difference in the insulin and glucose response to arginine stimulation suggesting a state of insulin resistance. The current study used this cohort of adult rats to evaluate insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], plasma adipokines (reflecting insulin resistance states), and testosterone. The major findings were that daily maternal-neonatal separation led to an increase in body weight and HOMA-IR in adult male and female rats and increased plasma leptin in adult male rats only; neither prior neonatal hypoxia (without or with body temperature control) nor neonatal hypothermia altered subsequent adult HOMA-IR or plasma adiponectin. Adult male-female differences in plasma leptin were lost with prior exposure to neonatal hypoxia or hypothermia; male-female differences in resistin were lost in the adults that were exposed to hypoxia and spontaneous hypothermia as neonates. Exposure of neonates to daily hypoxia without spontaneous hypothermia led to a decrease in plasma testosterone in adult male rats. We conclude that neonatal stressors result in subsequent adult sex-dependent increases in insulin resistance and adipokines and that our rat model of prematurity with hypoxia without hypothermia alters adult testosterone dynamics.


2020 ◽  
Vol 36 (7) ◽  
pp. 502-513
Author(s):  
Işil Aydemir ◽  
Caner Özbey ◽  
Oktay Özkan ◽  
Şadiye Kum ◽  
Mehmet İbrahim Tuğlu

Bisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 µg/kg BPA), and high dose (900 µg/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats’ lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.


2012 ◽  
Vol 126 (1) ◽  
pp. 195-195
Author(s):  
Tehila Eilam-Stock ◽  
Peter Serrano ◽  
Maya Frankfurt ◽  
Victoria Luine

2011 ◽  
Vol 36 (8) ◽  
pp. 1344-1352 ◽  
Author(s):  
Rasiah Pratheepa Kumari ◽  
Kandaswamy Selvakumar ◽  
Senthamilselvan Bavithra ◽  
Rafiq Zumaana ◽  
Gunasekaran Krishnamoorthy ◽  
...  

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