Androgen-linked control of rat liver carbonic anhydrase III

1983 ◽  
Vol 3 (5) ◽  
pp. 475-478 ◽  
Author(s):  
A. Shiels ◽  
S. Jeffery ◽  
I. R. Phillips ◽  
E. A. Shephard ◽  
C. A. Wilson ◽  
...  

The concentration of carbonic anhydrase IlI (CAIII) in male rat liver was found to be 30 times greater than that in the female. Castration of male rats led to marked reduction in liver CAIII concentrations which could be partially restored to control levels by testosterone replacement. Marked developmental and senescence changes in liver CAIII were also observed in male rats.

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.


2004 ◽  
Vol 181 (2) ◽  
pp. 223-231 ◽  
Author(s):  
V Viau ◽  
MJ Meaney

Hypothalamic-pituitary-adrenal (HPA) activity is governed by glucocorticoid negative feedback and the magnitude of this signal is determined, in part, by variations in plasma corticosteroid-binding globulin (CBG) capacity. Here, in gonadectomized male rats we examine the extent to which different testosterone replacement levels impact on CBG and HPA function. Compared with gonadectomized rats with low testosterone replacement ( approximately 2 ng/ml), plasma adrenocorticotropin and beta-endorphin/beta-lipotropin responses to restraint stress were reduced in gonadectomized rats with high testosterone replacement ( approximately 5 ng/ml). Plasma CBG levels also varied negatively as a function of testosterone concentration. Moreover, glucocorticoid receptor binding in the liver was elevated by higher testosterone replacement, suggesting that testosterone acts to enhance glucocorticoid suppression of CBG synthesis. Since pituitary intracellular CBG (or transcortin) is derived from plasma, this prompted us to examine whether transcortin binding was similarly responsive to different testosterone replacement levels. Transcortin binding was lower in gonadectomized rats with high plasma testosterone replacement ( approximately 7 ng/ml) than in gonadectomized rats with low testosterone replacement ( approximately 2 ng/ml). This testosterone-dependent decrease in pituitary transcortin was associated, in vitro, with an enhanced nuclear uptake of corticosterone. These findings indicate that the inhibitory effects of testosterone on corticotrope responses to stress may be linked to decrements in plasma and intrapituitary CBG. This could permit greater access of corticosterone to its receptors and enhance glucocorticoid feedback regulation of ACTH release and/or proopiomelanocortin processing.


1991 ◽  
Vol 284 (2) ◽  
pp. 270-278 ◽  
Author(s):  
Yuh-Cherng Chai ◽  
Che-Hun Jung ◽  
Chong-Kuei Lii ◽  
Syed S. Ashraf ◽  
Suzanne Hendrich ◽  
...  

1990 ◽  
Vol 266 (1) ◽  
pp. 69-74 ◽  
Author(s):  
S Jeffery ◽  
N D Carter ◽  
R G Clark ◽  
I C A F Robinson

Carbonic anhydrase III (CAIII) occurs in male rat liver at concentrations twenty times those in the female, and is sensitive to the pattern of growth hormone (GH) release. Males release GH episodically and have high concentrations of CAIII; females produce GH in a more continuous fashion and have lower CAIII levels. In normal female rats, the endogenous GH secretory pattern was masculinized, either by regular injections of GH-releasing factor (GRF) or by intermittent infusions of somatostatin (90 min on/90 min off). Both treatments induced regular GH pulses and stimulated growth, but only intermittent somatostatin infusions raised CAIII levels (controls, 1.5 +/- 0.5; somatostatin-treated, 9.0 +/- 2.9 micrograms/mg; means +/- S.D.). GRF pulses (4 micrograms every 4 h) did not however raise CAIII levels (controls 1.8 +/- 0.5; GRF-treated 1.4 +/- 0.4 micrograms/mg). Surprisingly, hepatic CAIII is also sexually dimorphic (males, 18.8 +/- 3; females, 2.22 +/- 0.4 micrograms/mg) in a GH-deficient dwarf rat strain which has low plasma GH levels without 3-hourly GH peaks. Intermittent somatostatin infusions in female dwarf rats partially masculinized hepatic CAIII, an effect reduced by co-infusion with GRF. This CAIII response was not secondary to growth induction, since neither somatostatin nor GRF stimulated growth in dwarf rats, and pulses of exogenous GH stimulated growth in female dwarfs without masculinizing CAIII levels. Furthermore, continuous GH infusion in male dwarf rats partially feminized hepatic CAIII levels (to 9.1 +/- 2.4 micrograms/mg), whereas infusions of insulin-like growth factor-1, which induced the same body weight gain, did not affect hepatic CAIII (20.8 +/- 6 micrograms/mg). These results show that hepatic CAIII expression is highly sensitive to the endogenous GH secretory pattern, independent of growth. They also implicate the low basal GH levels between pulses, rather than the peak GH levels, as the primary determinant of the sexually dimorphic hepatic CAIII expression in the rat.


Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 408
Author(s):  
Alexander M. Mathes ◽  
Paul Heymann ◽  
Christian Ruf ◽  
Ragnar Huhn ◽  
Jochen Hinkelbein ◽  
...  

Melatonin receptors are highly relevant for the hepatoprotective effects of the pineal hormone melatonin after experimental hemorrhagic shock in rats. In this study, we sought to determine the spatial expression pattern and a putative regulation of two melatonin receptors, membrane bound type 1 and 2 (MT1 and MT2), in the liver of rats. In a male rat model (Sprague Dawley) of hemorrhage and resuscitation, we investigated the gene expression and protein of MT1 and MT2 in rat liver by utilizing real-time quantitative polymerase chain reaction, a western blot analysis, and immunohistochemistry. Plasma melatonin content was measured by an enzyme-linked immunosorbent assay. Male rats underwent hemorrhage and were resuscitated with shed blood and a Ringer’s solution (n = 8 per group). After 90 min of hemorrhage, animals were given vehicle, melatonin, or ramelteon (each 1.0 mg/kg intravenously). Sham-operated controls did not undergo hemorrhage but were treated likewise. Plasma melatonin was significantly increased in all groups treated with melatonin and also after hemorrhagic shock. Only MT1, but not the MT2 messenger ribonucleic acid (mRNA) and protein, was detected in the rat liver. The MT1 protein was located in pericentral fields of liver lobules in sham-operated animals. After hemorrhagic shock and treatment with melatonin or ramelteon, the hepatic MT1 protein amount was significantly attenuated in all groups compared to sham controls (50% reduction; p < 0.001). With respect to MT1 mRNA, no significant changes were observed between groups (p = 0.264). Our results indicate that both endogenous melatonin exposure from hemorrhagic shock, as well as exogenous melatonin and ramelteon exposure, may attenuate melatonin receptors in rat hepatocytes, possibly by means of desensitization.


1956 ◽  
Vol 34 (1) ◽  
pp. 903-911
Author(s):  
J. D. McColl ◽  
J. M. Parker ◽  
J. K.W. Ferguson

The diuretic response of the male and the female rat to aminophylline has been studied when these animals were pretreated with various concentrations of sodium chloride solution. A linear log dose – response curve was obtained over the dose range employed with male rats pretreated with 0.45% and 2% saline. Male rats exhibited a diuresis with 4% saline which was not increased by aminophylline. Female rats showed diuresis but the responses were more variable for almost all combinations of electrolyte load and xanthine dose. When they were pretreated with 0.45% and 2% saline, aminophylline caused some additional production of urine but this was much less regular than that observed with males. The variation in response to aminophylline after 4% saline was very marked but the trend suggested that the xanthine had a diuretic effect at the high dose. The diuretic responses to a xanthine, a mercurial, and a carbonic anhydrase inhibitor type of diuretic were compared in the male rat. Peak responses were smallest after the mercurial diuretic and greatest with the carbonic anhydrase inhibitor.


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