The effect of dexamethasone, diet control and hyperglycemia on murine hepatic T3 receptors

Kenneth D. Burman, Yvonne D. Lukes, Keith R. Latham, Allan R. Glass, Robert C. Smallridge, Leonard Wartofsky

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6 Scopus citations

Abstract

There exists an apparent relationship between thyroid hormones and other substrates known to influence carbohydrate homeostasis. Thyroid hormones, for example, increase lipolysis in rat adipocytes in response to glucagon, and reciprocally, T3 administration increases glucagon receptors and thus stimulates glycerol production. In order to further study these relationships we determined whether dexamethasone, streptozotocin-induced diabetes, glucose feeding and carbohydrate content of diet altered murine hepatic nuclear T3 receptors. Rats were divided into one of several protocols:(1) dexamethasone was administered i.p. at a dose of approximately 1.5 mg/kg for 6-10 days, (2) streptozotocin was administered in a dose of approximately 65 mg/kg and the rats were sacrificed and the nuclei studied approximately 7-10 days later. Mean (± SE) plasma glucose at the time of sacrifice was 539 ± 33 mg/dl (n=5) in the streptozotocin treated rats and 159 ± 8 mg/dl (n=5) in the saline injected control animals; (3) in the glucose studies, rats were divided into either a fasted group, a fasted group that was given 50% dextrose in their drinking water or into a group allowed to eat normally. These groups were given the appropriate diet for 3 days at which time they were sacrificed; (4) to assess the effect of carbohydrate content of the diet, rats were pair fed and allowed to eat either a diet containing 79% carbohydrate, 9% protein and 5% fat or a diet containing 52% carbohydrate, 36% protein and 5% fat. The diets contained adequate amounts of all other necessary nutrients. Rats were sacrificed after ingesting either of these diets for approximately 14 days. In all studies, hepatic nuclei were isolated and studied as previously reported (Endocrinology 107:1081, 1980). In dexamethasone treated rats, the maximal percentage binding of 125 I-T3 per mg DNA was 18.8 ± 2.8 (n=4) in normal non-injected rats, 21.2 ± 5.7 (n=7) in saline injected rats and 16.8 ±3.9 (n=7) in dexamethasone injected rats. The difference between the saline injected and dexamethasone injected rats was statistically significant (p<0.05). The maximal binding capacity (MBC) expressed as pmoles/mg DNA was 0.392 ± 0.079 in normal rats, 0.456 ± 0.105 in saline injected rats, and 0.317 ± 0.067 in dexamethasone treated rats. The Ka values (X108M-1) were 4.5 ± 0.5, 6.2 ± 1.2 and 5.1 ± 0.7 in the three groups, respectively. In the streptozotocin treated rats, the maximal percentage 125I-T3 binding per mg DNA was 18.9 ± 5.8 (n=6) and this was decreased slightly but significantly (p<0.025) to 16.0 ± 5.8 in the diabetic rats. As expected, fasting was associated with a decreased MBC (pmoles/mg DNA) when compared to normal fed rats (0.667 ± 0.510, fast vs. 0.849 ± 0550, fed). Glucose administration in the drinking water to fasting rats, however, did not alter the MBC (0.650 ± 0.500) compared to that in fasting. Unstimulated or T3 stimulated alpha-GPD activity was also measured in these 3 groups of rats and was not different in any group studied. Lastly, several groups of studies were performed in the rats ingesting either a 79% or a 52% carbohydrate diet. The MBC (pmoles/mg DNA) was 0.39 ± 0.05 (n=10) in the high carbohydrate group and 0.31 ± 0.05 (n=10) (p<0.05) in the low carbohydrate group. Since this difference was so slight, however, we restudied a separate group of rats utilizing an identical protocol except that the MBC was determined on solubilized nuclei. In these studies, there was no significant difference in the MBC in the two groups,. In conclusion, our data suggests that: (1) dexamethasone slightly decreases the T3 MBC; (2) Streptozotocin-induced diabetes decreases the 125I-T3 bound to hepatic nuclei; (3) T3 MBC decrease during fasting, and glucose feeding to fasting rats does not increase the MBC; (4) rats ingesting a 79% carbohydrates diet have a slightly higher T3 MBC than rats ingesting a 52% carbohydrate diet. This effect is very slight and not reproducible depending on the method of study of 125I-T3 binding and; (5) both unstimulated and T3 stimulated mitochondrial alpha-GPD activity are unchange in rats that are fasted, fasted plus given glucose, or normal fed.

Original languageEnglish (US)
Pages (from-to)1701-1712
Number of pages12
JournalLife Sciences
Volume28
Issue number15-16
DOIs
StatePublished - Jan 1 1981

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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