Hepatic estrogen and androgen receptors and binding proteins in streptozotocin-diabetic male Wistar rats.
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. 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 micrograms/kg s.c. daily; ovine growth hormone: 0.02 U/h s.c., 30 micrograms s.c. 7 times daily, 30 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Smith
D R
DR
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Rodway
M R
MR
Haniak
W A
WA
Bellward
G D
GD
D000818:Animals; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007328:Insulin / Q000627:therapeutic use; D008099:Liver / Q000032:analysis*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D011965:Receptors, Glucocorticoid / Q000032:analysis; D012737:Sex Factors
D007328:Insulin; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D003345:Corticosterone