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UBC Theses and Dissertations

The high affinity-low capacity androgen binding protein in the hepatic cystol of streptozotocin diabetic Wistar rats Rodway, Marie R.


Recently several groups have identified and partially characterized a high affinity-low capacity androgen binding protein (HALC ABP) in the hepatic cytosol of rats, rabbits and humans. In order to further characterize and to identify the physiological control mechanisms of this protein we did a series of studies in Wistar rats. The synthetic androgen methyltrienolone (R1881) was used as the ligand in binding studies. Precipitation with 50% ammonium sulfate resulted in a 2 to 3 fold purification, but did not eliminate the glucocorticoid receptor to which R1881 also binds. Frozen storage, at -80°C has no apparent effect on the hepatic HALC ABP. Studies on sex and age differences showed that R1881 binding was present in mature females and immature rats at less than one-half the concentration found in mature males. Neonatal castration of males appears to decrease or eliminate the HALC ABP in mature rats. No evidence of binding of R1881 to androgen binding proteins in blood was seen . The HALC ABP binding capacity was significantly reduced from control levels in 4 and 10 day streptozotocin (STZ, 60 mg/kg, intravenous) diabetic male Wistar rats; there are no apparent changes in Kd or in steroid specificity. After induction of diabetes with STZ, serum insulin levels are significantly decreased in 24 hours-Testosterone serum levels and triiodothyronine serum levels are significantly decreased 3 days after STZ injection. Dampening of the normal peaks of growth hormone secretion in male rats is evident 18 hours after STZ injection, and continues progressively. These changes correspond to the decrease in binding capacity of the hepatic HALC ABP. If the HALC ABP were regulated by one of these hormones, restoration of their serum levels should have restored the binding capacity of the HALC ABP. Partial restoration of the binding capacity of the prostatic androgen receptor was possible with testosterone or insulin in STZ diabetic rats. Attempted restoration to control levels of the hepatic HALC ABP by treatment of 4 day STZ diabetics with the following hormones was unsuccessful: insulin (protamine zinc insulin, 10 U/kg s.c. daily, or Toronto insulin 15 U/kg s.c. twice daily); testosterone enanthate (1 mg/kg s.c. daily); triiodothyronine (30 μg/kg s.c. daily); or ovine growth hormone (by minipump 0.02 U/hr for 4 days, s.c. 30 μg/dose for 7 daily doses, vena cava catheter 30 μg/dose for 7 daily doses, and tail vein injection 30 μg/dose, for 4 daily dose s). It is concluded that the HALC ABP is not regulated by insulin levels, by testosterone levels, by T₃ levels, or by GH levels or the GH male secretory pattern. Stress appears to cause a decrease in the binding capacity of the HALC ABP in adult male Wistar rats.

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