scholarly journals Effect of age, gonadectomy and hypophysectomy on mitochondrial hydroxylation of vitamin D3 (cholecalciferol) and of 5β-cholestane-3α,7α,12α-triol in female and male rat liver

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.


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.


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.


1973 ◽  
Vol 72 (1) ◽  
pp. 1-8 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper

ABSTRACT It has previously been shown that the activity of certain peptidases in the female rat hypothalamus is related to the release of luteinizing hormone releasing factor from the tissue (Griffiths & Hooper 1972a). The activity of these enzymes was investigated after orchidectomy and testosterone propionate injection to determine if a similar relationship exists in male rats. The depression in supernatant activity following orchidectomy and the elevation after testosterone treatment are interpreted as confirming this, and it is proposed that alterations in peptidase activity may be used as an index of gonadotrophin release in male as well as in female rats.


1961 ◽  
Vol 200 (3) ◽  
pp. 519-522 ◽  
Author(s):  
David Kritchevsky ◽  
Ezra Staple ◽  
Joseph L. Rabinowitz ◽  
Michael W. Whitehouse

Female rat liver mitochondria oxidized cholesterol-26-C14 and sodium pyruvate-2-C14 to C14O2 to a much greater extent (per mg N) than did male rat liver mitochondria. Mitochondrial preparations from livers of castrated, estrogenized or castrated-estrogenized male rats all oxidized cholesterol-26-C14 to a greater extent than did liver preparations from normal male rats. No differences were observed in the oxidation of sodium octanoate-1-C14. The serum and liver cholesterol levels of the feminized rats were higher than those of the intact males. Biosynthesis of cholesterol from sodium acetate-2-C14 by male rat liver homogenates was significantly lower than biosynthesis by liver homogenates from normal female rats or gonadectomized rats of both sexes. The rate of biosynthesis from mevalonic acid-2-C14 by liver homogenates from castrated male rats was much higher than in homogenates of oophorectomized females or intact males or females. Differences in sex or gonadectomy had no effect on biosynthesis of fatty acids from sodium acetate-2-C14.


1971 ◽  
Vol 67 (3) ◽  
pp. 517-530 ◽  
Author(s):  
Martin Wenzel

ABSTRACT With the aid of metenolon-17α-T a tritium-transfer to oestrone in rat liver slices was demonstrated. This tritium-transfer from metenolon17α-T to oestrone yielding tritium-labelled oestradiol had a higher efficiency in male than in female rat liver. Correspondingly in the presence of metenolon the relation of oestrone to oestradiol is changed more in male than in female rat liver. Looking for biochemical differences between the anabolic steroid metenolon and testosterone the oxydation at C17 was measured in different organs of the rat using 17α-T-labelled steroids. The highest oxydation rate was found for both steroids in the liver. In the sexual organs of male rats the oxydation rate of testosterone was 50–10 times higher than that of the anabolic steroid. This difference was less in sexual organs of female rats. This result of a greater biochemical difference between both steroids in males than in females leads to the question, whether the dissociation between the anabolic and the androgen effects is higher in males than in females.


1986 ◽  
Vol 250 (1) ◽  
pp. 120-127 ◽  
Author(s):  
Myrtle Thierry-Palmer ◽  
Suzanne Cullins ◽  
Shakoora Rashada ◽  
T.Kenney Gray ◽  
Almena Free

1990 ◽  
Vol 5 (3) ◽  
pp. 267-274 ◽  
Author(s):  
I. Porsch Hällstöm ◽  
J.-Å. Gustafsson ◽  
A. Blanck

ABSTRACT Expression of the c-myc gene was studied in the livers of male and female Wistar rats. Furthermore, the effects on hepatic c-myc expression of neonatal and adult castration, with or without testosterone supplementation, as well as of continuous administration of GH to intact males, were analysed. Expression of c-myc was low in 6-day-old animals of both sexes, reached a maximum at 35 days of age and declined to the level of adult animals at 70 days. In prepubertal animals, expression was higher in females, but was higher in males after the onset of puberty, the postpubertal female rat liver exhibiting 50–70% of the expression in males. Treatment of adult male rats with bovine GH in osmotic minipumps for 1 week reduced c-myc expression to the level of female rats. Castration, both neonatally and of adults, also feminized hepatic c-myc expression. Testosterone supplementation of the castrated animals increased the expression towards the level in sham-operated controls. These results indicate that the c-myc gene is regulated by the hypothalamo-pituitary-liver axis via the sex-differentiated pattern of GH secretion, in analogy with other sex-differentiated hepatic functions, such as metabolism of steroids and xenobiotics. Neuroendocrine regulation of a gene such as c-myc, which is involved in the control of cell proliferation and differentiation, represents another aspect of the complex influence of GH on various somatic functions.


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.


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