ISSN:
1432-0428
Keywords:
Streptozotocin
;
diabetes
;
liver
;
estrogen receptor
;
androgen receptor
;
high capacity-low affinity estrogen binding protein
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary We have previously shown that there are decreases in the sex differences seen in certain hepatic drug and steroid metabolising enzymes in rats with early (4 day) streptozotocin-induced diabetes [31]. We postulated that hepatic sex hormone receptors or binding proteins might be involved in modulation of the sex differences noted in metabolism. In the present study, we measured the binding kinetics of the hepatic cytosolic estrogen receptor and androgen receptor, along with the high capacity-low affinity estrogen binding protein. At 4 or 10 days post-streptozotocin (60 mg/kg intravenously), there was no change in the maximum binding capacity of the estrogen receptor, nor in the hormone affinity of any of the three proteins. However, the binding capacity of the androgen receptor and estrogen binding protein in the diabetic animals was decreased to less than half of control levels. This effect could not be reversed by hormone replacement with any of the following regimens: protamine zinc insulin, 10 U/kg subcutaneously once a day; Toronto insulin, 15 U/kg subcutaneously twice a day; testosterone enanthate, 1 mg/kg s.c. once a day; triiodothyronine, 30 μg/kg s.c. daily; ovine growth hormone: 0.02 U/h s.c., 30 μg s.c. 7 times daily, 30 μg i.v. 4 times daily; or various combinations of these hormones. Stress, such as 4 intravenous injections of saline per day, was noted to decrease the binding capacity of the estrogen binding protein. Therefore, we measured the basal serum corticosterone levels, which were not significantly different from control values in untreated or insulin-treated diabetic rats. In addition, the hepatic cytosolic glucocorticoid receptor capacity was not significantly changed in the diabetic animals. This provides evidence that at 4 days post-streptozotocin, the diabetic state is not so stressful as to result in major alterations in these two parameters. In summary, because insulin is known to restore the sex differences in hepatic drug and steroid metabolism to control levels but does not restore the capacity of the cytosolic androgen receptor or estrogen-binding protein, we conclude that they are not of primary importance in regulation of the metabolic enzymes.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00295881
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