scholarly journals Metabolism of a glutathione conjugate of 2-hydroxyoestradiol-17β in the adult male rat

1972 ◽  
Vol 126 (5) ◽  
pp. 1067-1071 ◽  
Author(s):  
John S. Elce

Adult male rats with cannulated or ligated bile ducts were given S-(2-hydroxyoestradiol-1-yl)[35S]glutathione, S-(2-hydroxy[6,7-3H2]oestradiol-1-yl)glutathione or S-(2-hydroxyoestradiol-1-yl)[glycine-3H]glutathione by intraperitoneal injection. The recovery of radioactivity in the bile of bile duct-cannulated rats was 33–86% and in the urine of bile duct-ligated rats was 54–105%. Oestrogen thioether derivatives of glutathione, cysteinylglycine, cysteine and N-acetylcysteine were isolated from bile; only the N-acetylcysteine derivatives could be identified in the urine. The steroid moiety was characterized by microchemical tests before and after treatment with Raney nickel: 2-hydroxyoestradiol-17β was released from the glutathione conjugate, and 2-hydroxyoestrone and 2-hydroxyoestrone 3-methyl ether from the other conjugates. From intact rats the recovery of administered radioactivity was about 15% in the urine and 5% in the faeces over a period of several days and the radioactivity appeared to be largely protein-bound. The results demonstrate that injected oestrogen–glutathione conjugate undergoes conversion into N-acetylcysteine derivatives in vivo. Oestrogen–glutathione conjugates formed in the intact rat may be excreted in an apparently non-steroidal, possibly protein-bound form, which would not be detected by current analytical techniques.

1966 ◽  
Vol 20 (2) ◽  
pp. 339-347 ◽  
Author(s):  
R. J. L. Allen ◽  
J. S. Leahy

1. For 26 weeks, adult male rats were fed on diets containing about 80 % of carbohydrate, given as dextrose, fructose, liquid glucose, or sucrose; their performance was compared with that of rats receiving a standard laboratory cubed diet (41 B) containing 60 % of carbohydrate, mainly as starch. 2. More of diet 41 B was eaten than of any of the diets containing sugars, but only with dextrose was the mean body-weight gain significantly lower than with diet 41 B. 3. No significant differences in body length or girth were produced by the different diets. 4. Compared with those of rats given diet 41B, plasma cholesterol levels were significantly in- creased by fructose and sucrose and to a lesser extent by dextrose, but not by liquid glucose. 5. Compared with those given diet 41 B, the rats given fructose had heavier hearts, kidneys and livers, those given sucrose had heavier hearts and livers, and those given dextrose had heavier hearts. Those given fructose had the heaviest kidneys and livers, and heavier hearts than those given liquid glucose. The organ weights of those given liquid glucose and those given diet 41 B were not significantly different. 6. Compared with the values on diet 41B, carcass and liver fat were both significantly increased by sucrose and fructose but not by dex- trose or liquid glucose. With fructose, liver fat was almost double that with dextrose or liquid glucose. 7. Dry-matter contents of whole carcass and liver followed substantially the same pattern as did the fat contents. 8. Liver protein content was significantly lower on the 80 % carbohydrate diets. The reductions were greatest with fructose and sucrose.


1983 ◽  
Vol 97 (3) ◽  
pp. 401-407 ◽  
Author(s):  
A. S. McNeilly ◽  
D. W. Lincoln

To investigate the role of the pineal gland in the long-term suppression of gonadotrophin secretion induced by prolactin, the effects of pinealectomy were studied in adult male rats with hyperprolactinaemia produced by the transplantation of two pituitary glands under the kidney capsule. Pinealectomy had no effect on basal levels of LH, FSH or prolactin. The presence of pituitary transplants induced a significant twofold increase in prolactin levels and a prolonged suppression in both LH and FSH. These changes were not affected by pinealectomy. Castration resulted in a similar rise in plasma levels of LH and FSH in rats with and without pituitary transplants. In control rats this rise in LH and FSH was reduced by testosterone-containing silicone elastomer implants (s.c) of 10 mm in length and delayed by implants of 30 mm. These rises in LH and FSH were significantly delayed (10-mm implant) or abolished (30-mm implant) in rats with pituitary transplants indicating an increase in sensitivity of the hypothalamic-pituitary axis to the negative feedback effects of testosterone in these animals compared to controls. These responses were not affected by pinealectomy. These results suggest that the pineal gland is not involved in the mechanism whereby pituitary grafts, possibly through their secretion of prolactin, cause long-term suppression of gonadotrophin secretion.


1968 ◽  
Vol 40 (4) ◽  
pp. 397-408 ◽  
Author(s):  
J. F. BITHELL ◽  
K. BROWN-GRANT

SUMMARY The uptake of 131I by the thyroid gland of the castrated adult male rat is increased 24 hr. and is maximal 48 hr. after the injection of a single dose of 50 μg. oestradiol. The response is not dose-dependent between 25 and 1600 μg. The thyroid:serum (T:S) concentration ratio for 131I is also increased by oestradiol with a time-course similar to the changes in uptake, but release of 131I-labelled hormone from the gland in vivo and radioactive phosphate uptake were not affected. Analysis of the kinetics of 131I accumulation by the blocked gland show that the effects on 131I uptake and T:S ratio were due to an increase in the clearance rate with a possible associated decrease in the exit rate constant for iodide from the gland to the blood. Under the conditions of these experiments, the effects of oestradiol are not consistent with their being produced by an increase in pituitary thyrotrophic hormone secretion; a direct action on the gland appears likely. These conclusions apply solely to the experimental conditions described here and do not provide the basis for any generalization about the action of oestrogens on the thyroid gland. The method of analysis developed for the estimation of the unilateral clearance constant and the exit rate constant, together with their standard deviations, is presented in an appendix.


1970 ◽  
Vol 116 (5) ◽  
pp. 913-917 ◽  
Author(s):  
John S. Elce

Adult male rat liver and kidney preparations were incubated with (2-hydroxyoestradiol-1-yl)[35S]glutathione. The glutamic acid and glycine residues were removed by enzymes present in the kidney microsomal fraction; the liver preparations had no effect. The resulting 2-hydroxyoestradiol–cysteine conjugate was acetylated at the α-amino group by both liver and kidney homogenates fortified with acetyl-coenzyme A, but not significantly in the absence of this coenzyme, or by liver or kidney slices. These results suggest that an oestrogen–glutathione conjugate, if formed in vivo, would be converted into the corresponding mercapturic acid before excretion.


1973 ◽  
Vol 51 (12) ◽  
pp. 890-892 ◽  
Author(s):  
R. Collu ◽  
J. C. Jéquier ◽  
J. Letarte ◽  
G. Leboeuf ◽  
J. R. Ducharme

Brain levels of monoamines (MA) in the adult male rat show a diurnal pattern of secretion with noradrenaline (NA) and serotonin (5-HT) reaching a peak at 1300 and 1800, respectively, and dopamine (DA) showing a bimodal pattern with peaks at 0500 and 1800. Plasma growth hormone (GH) values fluctuate widely during the nycthemeral period. Statistically significant correlations between plasma GH and brain MA levels, confirming the existence of a physiological role of MA in the control of GH secretion, could not be demonstrated in the present study.


2020 ◽  
Vol 26 (3) ◽  
pp. 509-523 ◽  
Author(s):  
Amany Mohamed Shalaby ◽  
Adel Mohamed Aboregela ◽  
Mohamed Ali Alabiad ◽  
Dina Fouad El Shaer

AbstractTramadol is a centrally acting analgesic drug, used for the management of moderate to severe pain in a variety of diseases. The long-term use of tramadol can induce endocrinopathy. This study aimed to evaluate the effect of tramadol dependence on the adrenal cortex and the effect of its withdrawal. Thirty adult male rats were divided into three experimental groups: the control group, the tramadol-dependent group that received increasing therapeutic doses of tramadol orally for 1 month, and the recovery group that received tramadol in a dose and duration similar to the previous group followed by a withdrawal period for another month. Specimens from the adrenal cortex were processed for histological, immunohistochemical, enzyme assay, and quantitative real-time PCR (RT-qPCR) studies. Tramadol induced a significant increase in malondialdehyde level and a significant decrease in the levels of glutathione peroxidase and superoxide dismutase. A significant decrease in the levels of adrenocorticotrophic hormones, aldosterone, cortisol, corticosterone, and dehydroepiandrosterone sulfate was also detected. Severe histopathological changes in the adrenal cortex were demonstrated in the form of disturbed architecture, swollen cells, and shrunken cells with pyknotic nuclei. Inflammatory cellular infiltration and variable-sized homogenized areas were also detected. A significant increase in P53 and Bax immunoreaction was detected and confirmed by RT-qPCR. The ultrastructural examination showed irregular, shrunken adrenocorticocytes with dense nuclei. Dilated smooth endoplasmic reticulum, mitochondria with disrupted cristae, and numerous coalesced lipid droplets were also demonstrated. All these changes started to return to normal after the withdrawal of tramadol. Thus, it was confirmed that the long-term use of tramadol can induce severe adrenal changes with subsequent insufficiency.


1970 ◽  
Vol 120 (2) ◽  
pp. 409-416 ◽  
Author(s):  
Prabhakar D. Lotlikar

1. Enzymic esterifications of 2-(N-hydroxyacetamido)fluorene and several other hydroxamic acids by liver cytosol were studied. Determination of 2-acetamido-3-methylthiofluorene was used for the assay. 2. With rat liver cytosol, requirement for ATP, Mg2+ and SO42− suggested formation of phosphate and sulphate esters of 2-(N-hydroxyacetamido)fluorene. 3. Rats showed sex and age differences in their activity. Liver from adult male rat was at least twice as active as liver from adult female rat. No such sex differences were found in mice, hamsters and guinea pigs. 4. Administration of testosterone (300μg/day) subcutaneously for 8 days increased the activity in the female rat by 100%, whereas diethylstilboestrol (100μg/day) had no effect. In the male rat diethylstilboestrol treatment decreased the activity by 60%, whereas testosterone pretreatment was without any effect. 5. Among various endocrine ablations such as adrenalectomy, castration, adrenalectomy–castration and hypophysectomy in the adult male rat, hypophysectomy was found to be the most effective in decreasing the activity of the liver to about 50% of control values. 6. Like 2-(N-hydroxyacetamido)fluorene, various other N-hydroxy derivatives of 2-acetamido-7-fluorofluorene, 2-acetamidophenanthrene, 4-acetamidobiphenyl and 4-acetamidostilbene were also shown to be esterified to different extents by rat liver cytosol.


1975 ◽  
Vol 80 (3) ◽  
pp. 583-591 ◽  
Author(s):  
R. W. Hall ◽  
W. R. Gomes

ABSTRACT Oestrone, oestradiol and testosterone levels were measured by radioimmunoassay in male rats 0.5, 1, 4, 8 and 16 days after rats were either made artificially cryptorchid or sham-operated. Oestradiol levels were not significantly different between cryptorchid and control rats 12 h or 1 day after surgery, but levels in cryptorchid animals fell to 35 % of controls on day 4 (P < 0.05), 31% on day 8, and 29% on day 16 (P < 0.01). Conversely, oestrone and the total of the two oestrogens was higher in cryptorchid rats at one-half day (P <0.05), but did not differ at any other time. Testosterone levels were generally lower in cryptorchid rats than in controls. The minor contribution of oestradiol to total oestrogen levels and the lack of change of total oestrogens in cryptorchid rats led to the conclusion that oestrogens are probably not the tubular regulator of FSH in the male.


1974 ◽  
Vol 77 (4) ◽  
pp. 643-654 ◽  
Author(s):  
H. L. Verjans ◽  
K. B. Eik-Nes ◽  
J. H. Aafjes ◽  
F. J. M. Vels ◽  
H. J. van der Molen

ABSTRACT The influence of treatment with various doses of testosterone propionate, 5α-dihydrotestosterone propionate or oestradiol benzoate on serum levels of LH and FSH (measured by radioimmunoassay) and on weights of ventral prostates and seminal vesicles was investigated in castrated, adult, male rats. For depression of the high, castrate levels of serum gonadotrophins with either of these steroid esters, the inhibition curves were different for LH and for FSH. Serum LH was kept at levels encountered in intact, adult, male rats by lower doses of steroid ester than was serum FSH. Oestradiol benzoate was the most potent suppressor of the serum gonadotrophins among the steroid esters tested, testosterone propionate the least. Treatment with low doses of oestradiol benzoate, however, resulted in serum FSH levels significantly above those of castrates treated with vehicle only. Finally, administration of a synthetic LH-releasing factor to testosterone propionate, 5α-dihydrotestosterone propionate or oestradiol benzoate treated, castrated, adult, male rats resulted in a further release of both LH and FSH. The latter effect was more pronounced in oestradiol benzoate treated castrates than in testosterone propionate or 5α-dihydrotestosterone propionate treated castrates.


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