Liver Selenium and Testis Phospholipid Hydroperoxide Glutathione Peroxidase Are Associated with Growth during Selenium Repletion of Second-Generation Se-Deficient Male Rats

Abstract

We have previously shown that changes in glutathione peroxidase-1 (GPX1; H2O2:oxidoreductase, EC 1.11.1.9), plasma thyroid hormone and glutathione-S-transferase were not associated with changes in growth observed in second-generation (F2) severely Se-deficient rats; we also found that liver phospholipid hydroperoxide glutathione peroxidase (GPX4; EC 1.11.1.12) activity falls in first-generation (F1) Se-deficient rats to 41% of levels in Se-adequate rats. The purposes of this study were to determine the effect of F2 Se deficiency on GPX4 and to detect early changes in Se parameters associated with growth after single, small Se injections. Se-deficient male F2 weanling rats were randomly divided into two groups and fed a Se-deficient crystalline amino acid (0.003 μg Se/g diet; −Se) diet or that diet supplemented for 14 d with 0.2 μg Se/g diet (+Se) as Na2SeO3. Growth of −Se rats was 55% of the rate of +Se rats. Liver Se, GPX1 activity, GPX4 activity and testis GPX4 activity in −Se rats at 14 d were 1, 2, 23 and 13%, respectively, of levels in +Se rats. In a series of experiments, additional F2 male weanling rats were fed the −Se diet for 14 d and then were given an intraperitoneal single saline injection of 0, 1 or 5 μg Se/100 g body weight (BW) as Na2SeO3 and killed 1 or 7 d later. Rats injected with 1 or 5 μg Se/100 g BW grew 36 or 48%, respectively, above the rate of saline-injected rats. Liver Se concentration increased 367% and testis GPX4 activity doubled in rats 1 d after injection of 1 μg Se/100 g BW compared with saline-injected rats; these parameters were further elevated with 5 μg Se/100 g BW injections. Increases in liver Se and testis GPX4 activity were the parameters best associated with improved growth after Se injection, but the molecular role for Se in growth remains unclear.