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The effect of streptozotocin-induced diabetes on the male Wistar rat : hepatic high capacity, low affinity estrogen binding protein

University of British Columbia

Several parallels have been noted between aryl hydrocarbon hydroxylase (AHH) activity (a measure of drug and steroid metabolism) and the high capacity low affinity (HCLA) estrogen binding protein. These include a sex and age dependency, as well as parallel changes in the AHH and HCLA levels due to various physiological manipulations (e.g. gonadectomy and hypophysectomy). It has been suggested from this evidence that there is a regulatory action of the HCLA estrogen binding protein on hepatic AHH activity. Since streptozotocin (STZ) induced diabetes is known to cause alterations in AHH activity we investigated the effects of this condition on the HCLA estrogen binding protein, and sought the hormonal control mechanism for the HCLA estrogen binding protein in this state. At both four and ten days post-induction of diabetes with STZ, there was approximately a 50% decrease in the binding capacity of the HCLA estrogen binding protein, with no alterations in the Kd value. Hormonal replacement was undertaken to restore the normal physiological levels of testosterone, insulin, triiodothyronine, and growth hormone; all of which are depressed in the diabetic. None of the treatment regimens carried out were able to restore the reduced binding capacity of the HCLA binding protein. Treatment with testosterone and insulin had previously been shown to restore AHH activity in gonadectomized and diabetic rats, respectively. Since we were unable to restore HCLA binding protein levels with these treatments in the diabetic rat, we conclude that there is no direct regulatory action of the HCLA binding protein on AHH activity in the rat. Several other species were also examined for the presence of a hepatic HCLA estrogen binding protein. We were unable to detect any such component in any of the other species examined, indicating that the HCLA binding protein may be rat specific. What physiological role the HCLA binding protein may be playing remains unclear at this time.

Text

2010-06-30

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http://hdl.handle.net/2429/26078

Pharmaceutical Sciences

University of British Columbia

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