Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 26, 1999
Publication Date: N/A
Interpretive Summary: Thyroid status of growing animals is an important regulator of metabolic rate and affects the amount of nutrients used for maintenance and growth. Whereas prohormone thyroxine (T4) is synthesized only in the thyroid gland, triiodothyronine (T3), the most metabolically active thyroid hormone, is produced by enzymatic 5'-deiodination of the T4 within the thyroid and in extrathyroidal tissues. Therefore, the extrathyroidal activity of iodothyronine 5'-deiodinase (5'D) is an important control point for regulating the metabolic status of animal tissues in various physiological and pathological situations. In the present study we investigated in cattle the effect of a low dose endotoxin (LPS) challenge with and without L-arginine (Arg) infusion on hepatic 5'D activity and plasma concentrations of T4 and T3. Endotoxin is a model effector of the acute phase response of bacterial infection. Arginine supplementation has been reported previously yto improve the response to disease stress in experimental animals. We demonstrated that administration of a single low level dose of LPS in cattle decreased circulating concentrations of thyroid hormones followed by decreased activity of 5'D in liver. The time course of these changes indicates that decreased extrathyroidal T3 generation from T4 after LPS challenge is a secondary event caused by reduced thyroid gland activity. Although Arg infusion alleviated decreased 5'D activity in liver, it did not compensate for the depressed secretion of T3 from the thyroid gland. These results suggest that even mild bacterial infection in cattle significantly compromises thyroid status and, consequently, may affect growth rate.
Technical Abstract: Thyroid status is compromised in a variety of acute and chronic infections. Conversion of thyroxine (T4) into the metabolically active hormone, triiodothyronine (T3), is catalyzed by 5'-deiodinase (5'D). Our objective was to determine the effect of endotoxin (LPS) challenge with and without L-arginine (Arg) infusion on hepatic activity of 5'D and plasma concentrations of T4 and T3. In a 2 x 2 factorial, beef heifers (275-310 kg BW) were fed low (8% CP; 6.5 kg/d) or high (14% CP; 7.2 kg/d) isocaloric protein diets (1.96 Mcal/kg DM) for 10 d before LPS challenge. L-Arginine in saline (0.5 g/kg BW) or saline alone was infused i.v. throughout an 8 h period starting 2 h before bolus LPS injection (E. coli, 055:B5; 0.2 ug/kg; i.v.). Blood samples were collected at -2, 0, 3, 6, 12, and 24 h relative to LPS injection. Liver samples were obtained 20 h before, and then 6 and 24 h after LPS challenge using a biopsy needle. Plasma T4 and T3 concentrations were not affected by dietary CP or Arg. Compared with levels at 0 h, LPS challenge decreased plasma T4 (P < 0.01) and T3 (P < 0.001), respectively, 8.4% and 28.9% at 6 h and 19.7% and 31.3% at 24 h. Consistent with these changes, the T3:T4 ratio was lower than that at 0 h (P < 0.001) 22.0% at 6 h and 13.5% at 24 h. Hepatic 5'D activities 20 h before LPS injection were 2.80 (SE = 0.11) nmol I/(h x mg protein) and decreased 24 h after LPS, respectively, 45.4% (P <0.01) and 17.6% (P <0.05) in saline- and Arg-infused heifers. The results indicate that mild LPS challenge in cattle inhibits hepatic generation of T3 and decreases plasma concentrations of thyroid hormones. The data also suggest that the impact of LPS on 5'D activity in liver can be altered by Arg supplementation.