Thyroxine ′-Deiodination in Brown Adipose Tissue and Pineal Gland: Implications for Thermogenic Regulation and Role of Melatonin*

Abstract

T4 type II 5'-deiodinase (5'-D II) activity was studied in wild-captured Richardson's ground squirrels. As previously reported for other species, 5'-D II activity was detected in frontal cortex, cerebellum, pineal gland, and brown adipose tissue (BAT); in the median eminence the levels of 5'-D II activity were undetectable with our methodology. When pineal gland, frontal cortex, and cerebellum nyctohemeral profiles were studied, none of them showed variations. Cold exposure for 4 h led to an increase in the enzymatic activity 10-fold above the basal values for BAT, while in the pineal gland the values were doubled; cold exposure failed to change the 5'-D II activity in the frontal cortex. Acute melatonin treatment caused a 7-fold increase in 5'-D II activity in BAT, but did not affect enzyme activity in either the pineal gland or frontal cortex. The data indicate that 5'-D II in Richardson's ground squirrel shows classical localizations. Additionally, two new regulatory factors of 5'-D II are reported, i.e. melatonin for BAT and cold for the pineal gland.

Melatonin multiple effects on brown adipose tissue molecular machinery

“…Notably, Dio2 expression was already increased in neutral condition in melatonin‐treated rats. This possibly reinforces the essential participation of DIO2 in thermogenesis and melatonin regulatory role of this protein in BAT …”

“…DIO2 is also part of the activation pathway in BAT, as T3 increases Ucp1 transcription. Melatonin and Dio2 interact after cold exposure, as seen here both after CE and HFD, indicating that melatonin induced Dio2 expression to cope with the challenges. Absence of melatonin, on the contrary, generated fewer transcripts in comparison with the other groups, pointing to a less prepared tissue.…”

Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity

“…At that time, it is difficult to explain this apparent paradoxical effect in which there was an inversed relationship between circulating T 4 and the amount of BAT. In the follow‐up study, it was found that in Richardson ground squirrels, melatonin administration elevated the activity of BAT 5′‐D 2 sevenfold (172). This activation of 5′‐D 2 by melatonin has been confirmed in Syrian hamsters and it is tissue specific, i.e.…”

Modifying effect of pineal peptide hormones on the reactivity of rat thyroid gland to cooling

“…A good illustration is presented in the report of E. Tang et al [5], who observed elevation of the serum triiodothyronine (1"3), thyroxine (T4) , and thyroid stimulating hormone (TSH) in albino rats exposed to 4~ for 1 and 5 hours. Other investigators observed a 2-fold activation of T 4-deiodinase in rat pineal gland after 4-h cooling at 4~ attesting to enhanced utilization of thyroid hormones by pinealocytes in hypothermia [4].On the other hand, our previous studies on clinical (intraoperation biopsy specimens of human TG) and experimental material demonstrated the involvement not only of pineal indoles but also of pineal peptide hormones into regulation of thyroid function [1][2][3]. These data were obtained under normal temperature, while the role of pineal hormones in the regulation of adaptation of the hypothalamus-pituitary-thyroid system to cold stress has not been evaluated.…”