Effects of thyroid hormone deiodination on regulation of thyroid axis in undernourished rats

Abstract

The possible influence of hypothalamic and pituitary 5'-deiodinase II (5'-D-II) activity and 3,5,3'-triiodothyronine (T3) content on the modulation of thyroid-stimulating hormone (TSH) synthesis was studied. 1) Alterations in 5'-D-II activity and hypothalamic and pituitary T3 content produced by undernutrition were observed in fetal (21 days) and neonatal rats vs. controls. 2) After thyroidectomy, plasma TSH increased in both populations, undernourished and control, but pituitary TSH increased only in the former and not in the latter. The results obtained by giving small doses of thyroxine (T4; 0.5 micrograms/100 g body wt) to intact and thyroidectomized rats suggest a lower inhibitory effect by T4 on the pituitary in undernourished than in control rats. Although hypothalamic and pituitary 5'-D-II activity increased in both groups after thyroidectomy, the percentage increase was lower in undernourished vs. control rats, resulting in lower overall T3 content in tissues from undernourished animals. These studies on thyroid axis regulation show the in vivo regulation of TSH synthesis by hypothalamic and pituitary 5'-D-II activity and T3 content.

Fasting-Induced Increase in Type II Iodothyronine Deiodinase Activity and Messenger Ribonucleic Acid Levels Is Not Reversed by Thyroxine in the Rat Hypothalamus

“…They reported DII activity changes in perinatal rats that are exposed to food restrictions. Although in that study a different regimen of food restriction was employed, an increase in fetal DII activity was detected after 5 days of the restricted diet administered to the dams (28).…”

“…To date, no previous reports are available regarding DII activity in short term fasted adult rats. However, a recent report by Pascual-Leone et al (28) supports the idea that dietary restriction, at least in its initial phase, parallels elevations in hypothalamic DII activity. They reported DII activity changes in perinatal rats that are exposed to food restrictions.…”

Influence of type II 5′ deiodinase on TSH content in diabetic rats

“…Among all "euthyroid sick syndromes", undernutrition and diabetes show a common pattern at the cellular level: cell starvation due to the lack of nutrients or to their reduced utilization by the absence of insulin. Both, undernutrition and diabetes, considered as "low T3 syndromes", induce a significant reduction of serum T3 and T4, together with a fall in pituitary and plasma TSH (1,13,26,30,34) as opposed to the usual increase in plasma TSH observed in hypothyroidism. Pituitary a and~TSH and GH mRNA levels are decreased in restricted feeding, fasting and diabetes in rats (29).…”

“…The hepatic T4 to T3 conversion is impaired in diabetes and fasting (1,2,12,24,25,27,34). Diabetes induces a different adaptive pattern at the neuroendocrine level with a reduced hypothalamic TRH content (13) and release (7,30) as compared to undernutrition (26).…”

“…Although the role of insulin in thyroid hormone alterations is thought to be related to the reversal of altered glucose utilization (12), there is an intrinsic pituitary abnormality in uncontrolled diabetic patients that requires further investigation (40). We have previously suggested that the hypothalamic and pituitary 5'D-II activities and T3 concentrations seem to play an important role in the regulation of the pituitary content and plasma levels of TSH in rats undernourished from gestation (26). Whether the same regulatory pathway takes place in diabetic animals remains to be studied.…”