TABLE 1.
Se requirement hierarchy in growing rats1
| Biomarker | Extent of regulation (P-value)2 | Minimum requirement3 |
|---|---|---|
| μg Se/g diet | ||
| Conventional biomarkers | ||
| Growth | Low (0.99 ) | <0.01 |
| Muscle Gpx4 activity | Low (0.83) | <0.01 |
| Plasma Gpx3 activity | Very high (<0.0001) | 0.06 |
| Liver Gpx4 activity | Moderate (<0.0001) | 0.06 |
| Liver Txnrd activity | Very high (<0.0001) | 0.06 |
| Kidney Gpx4 activity | Moderate (<0.0001) | 0.07 |
| Liver Se concentration | Very high (<0.0001) | 0.08 |
| RBC Gpx1 activity | High (<0.0001) | 0.08 |
| Liver Gpx1 activity | Very high (<0.0001) | 0.09 |
| Kidney Se concentration | High (<0.0001) | 0.11 |
| Kidney Gpx1 activity | Very high (<0.0001) | 0.12 |
| Muscle Gpx1 activity | Very high (<0.0001) | 0.13 |
| Molecular biomarkers | ||
| Liver Gpx4 mRNA | Low (0.10) | <0.01 |
| Kidney Gpx4 mRNA | Low (0.36) | <0.01 |
| Muscle Gpx4 mRNA | Low (0.99) | <0.01 |
| Kidney Sephs2 mRNA | Moderate up (0.008) | 0.02 |
| Muscle Gpx3 mRNA | Moderate (0.005) | 0.02 |
| Kidney Sepn1 mRNA | Moderate (0.04) | 0.02 |
| Liver Selk mRNA | High (<0.0001) | 0.03 |
| Liver Selt mRNA | Moderate (0.04) | 0.03 |
| Liver Gpx3 mRNA | High (0.005) | 0.04 |
| Liver Sepn1 mRNA | Moderate (0.007) | 0.04 |
| Liver Sepp1 mRNA | Moderate (0.0008) | 0.04 |
| Muscle Selh mRNA | Moderate (0.02) | 0.04 |
| Kidney Selh mRNA | High (<0.0001) | 0.05 |
| Muscle Sepw1 mRNA | High (0.04) | 0.05 |
| Muscle Gpx1 mRNA | High (0.14) | 0.05 |
| Liver Txnrd3 mRNA | Moderate (0.0004) | 0.05 |
| Kidney Selk mRNA | Moderate (0.0008) | 0.05 |
| Kidney Txnrd1 mRNA | Moderate (<0.0001) | 0.05 |
| Liver Selh mRNA | High (<0.0001) | 0.06 |
| Kidney Sepw1 mRNA | High (<0.0001) | 0.06 |
| Kidney Gpx1 mRNA | High (<0.0001) | 0.06 |
| Kidney Gpx3 mRNA | High (0.05) | 0.06 |
| Liver Sep15 mRNA | Moderate (0.01) | 0.06 |
| Liver Dio1 mRNA | Moderate (0.0002) | 0.06 |
| Liver Gpx1 mRNA | Very high (<0.0001) | 0.07 |
| Liver Sepw1 mRNA | High (<0.0001) | 0.07 |
Detailed statistical analyses are provided in Supplemental Tables 2 and 4 and values are shown for some biomarkers in Figures 1–3. Extent of Se regulation for all 24 rat selenoproteins for all tissues studied is provided in Supplemental Table 5.
Susceptibility to Se regulation of the indicated biomarker in Se-deficient rat tissue in Se-deficient compared with Se-adequate (0.24 μg Se/g diet) rats: very high = <10.9% of Se adequate; high = 11–40.9% of Se adequate; moderate = 41–70% of Se adequate; low = >70% of Se adequate; kidney Sephs2 mRNA is moderately upregulated in Se deficiency. Significance (P-value) of regulation indicated in parentheses.
Minimum dietary Se requirement for the growing rat as determined for each indicated biomarker in Expt. 2. Requirements are the minimum dietary Se necessary for the indicated parameter to reach plateau levels when Se-adequate weanling rats are fed these diets from weaning, as determined by breakpoint analysis as described in the text. Shown are all conventional biomarkers assessed in these studies, all molecular biomarkers that were significantly (P < 0.05) regulated by Se status, and all molecular biomarkers shown in Figure 3.