No abstract

Nephrotoxic agents such as puromycin aminonucleoside (PAN) and sodium maleate (MAL) have been used to induce experimental glomerular proteinuria and tubular disease, respectively. Current studies show that PAN caused a massive loss of albumin in the urine while not affecting the excretion of the smaller, sex-dependent α_2u-globulin. On the other hand, MAL which inhibits the reabsorption of proteins, increased the loss of both α_2u and albumin. Both nephrotoxic agents increased the excretion of albumin when administered to female rats. MAL-induced proteinuria was used as a direct measure of the renal load for α_2u and albumin. Renal loads and excretion of α_2u and albumin were measured in male rats maintained on 0, 20, and 50% casein diets. On the protein-free diet, the excretion of both α_2u and albumin was reduced (less than 1 mg daily); their renal loads were almost totally reabsorbed. On a 50% casein diet the reabsorption of α_2u was reduced from a normal of 60% to 10% of the renal load. Thus, the high protein diet increased the excretion of α_2u while having little effect on the excretion of albumin. We suggest that dietary protein exerts two levels of control on the excretion of protein in the urine of the adult male rat. Protein-deficient diets stimulate the general reabsorption of proteins thereby minimizing the excretion of α_2u and albumin. High protein diets appear to reduce selectively the reabsorption of α_2u -globulin, thereby increasing its excretion in the urine.

The hepatic synthesis of the androgen-dependent urinary protein in the rat, called alpha2u globulin, is strongly inhibited by estrogens. In mature male rats, treatment with estradiol-17beta (0.5 mug/g body weight) completely inhibits alpha2u synthesis within 6-7 days. Following withdrawal of estrogen treatment alpha 2u synthesis is not reinitiated for approximately 20 days. Parabiotic joining of estrogen-suppressed male rats with their normal littermates within this lag period fails to change the preparabiotic pattern of alpha2u synthesis in the respective partners. Besides estradiol-17beta, other estrane derivatives such as estrone, estriol and estradiol-17alpha were also found to inhibit the synthesis of alpha2u globulin. All of the above estrane derivatives which inhibit alpha2u synthesis are also found to inhibit the uptake of 5alpha-dihydrotestosterone by the hepatic cytosol androgen binding protein of the mature male rat. Unlike cycloheximide, a known translational inhibitor, estradiol-17beta does not inhibit alpha 2u synthesis in the perfused rat liver.

No abstract

Adult male rats were thyroidectomized and killed after 22 days of treatment. Thyroidectomy lowered the weights of testes and accessory sex organs, decreased the activities of testicular delta 5-3 beta- and 17 beta-hydroxysteroid dehydrogenases (HSD), and diminished spermatogenesis, serum levels of testosterone and alpha 2u-globulin. Supplementation with thyroxine at a dose of 5 micrograms/100 g body weight per day for 21 days or supplementation with alpha 2u-globulin at a dose of 1.5 mg/rat per day for 21 days in thyroidectomized animals partially reversed the decrease in HSD activities and serum concentrations of testosterone and alpha 2u-globulin, while spermatogenesis was restored to normal. The weights of testes and accessory sex organs were also reinstated after supplementation with thyroxine or alpha 2u-globulin in thyroidectomized rats in comparison with thyroidectomized animals. It was concluded that alpha 2u-globulin may be an intermediary in the thyroid hormone control of testicular function.