Interrelationships among thyroxine, growth hormone, and the sympathetic nervous system in the regulation of 5'-iodothyronine deiodinase in rat brown adipose tissue.

Abstract

Thyroxine (T4) and reverse triiodothyronine are potent inhibitors of brown adipose T4 5'-deiodinase (BAT 5D). This effect does not require protein synthesis and is due to an acceleration of the rate of disappearance of the enzyme. Growth hormone (GH) also inhibits BAT 5'D but by a mechanism mediated through a long-lived messenger that correlates with growth rate. This explains the failure of BAT 5D to increase abruptly after thyroidectomy as does the type II 5'-deiodinase in pituitary and central nervous system or the BAT 5'D itself after hypophysectomy. Although virtually inactive when given acutely, triiodothyronine replacement partially reduces BAT 5D in hypophysectomized and thyroidectomized (Tx) animals probably as a result of improvement of systemic hypothyroidism and an increase in GH levels in the Tx rats. The fine balance between these inhibitory factors and the stimulatory effects of the sympathetic nervous system suggests an important physiologic role for the enzyme in this tissue.

Effect of suckling and adrenergic stimulation on peripheral deiodination in lactating rats: differential expression of type 1 deiodinase mRNA forms

“…These findings coincide with previous reports showing that in a catabolic situation, such as lactation (Giralt et al 1987, Aceves et al 1994 or fasting (Silva & Larsen 1986), the sensibility of D2 BAT to NE is impaired. The exact mechanism implicated in this differential regulation is unknown; however, several studies suggest that the hormonal and nutritional 'milieu' characteristic of lactation (hypothyroidism, hypoglycemia, hypoinsulinemia, elevated concentrations of growth hormone, etc.)…”

“…The exact mechanism implicated in this differential regulation is unknown; however, several studies suggest that the hormonal and nutritional 'milieu' characteristic of lactation (hypothyroidism, hypoglycemia, hypoinsulinemia, elevated concentrations of growth hormone, etc.) could modulate the adrenergic outflow and response in different target tissues (Silva & Larsen 1986, Aceves et al 1994, Larsen & Berry 1995, Hernandez & Obregon 2000. Thus, whereas the increased sympathetic tone triggered by suckling may be responsible for maintaining the elevated heart and MG D1 activity observed in the present study, the impaired D2 BAT adrenergic response could be secondary to the accompanying hypothyroidism and the increased growth hormone levels that characterize lactation.…”

Thyroxine and tri-iodothyronine differently affect uncoupling protein-1 content and antioxidant enzyme activities in rat interscapular brown adipose tissue

“…On the other hand, BAT itself is a target for thyroid hormones and has a large number of 1 and 1 thyroid hormone receptors (Hernández & Obregón 1996). Since high plasma levels of T 4 inhibit D2 (Silva & Larsen 1986) it could be argued that the BAT of T 4 -hyperthyroid rats is really lacking in T 3 and, therefore, results obtained in T 4 -hyperthyroid rats cannot be attributed to an excess of T 3 in BAT (Ablenda & Puerta 1992). Knowing that UCP1 was predominantly affected by the occupancy of BAT nuclear T 3 receptors (Branco et al 1999), it is understandable why T 4 treatment, under basal conditions, does not enhance IBAT UCP1 content.…”

“…Since the SNS plays a much more significant role in nonshivering thermogenesis at any temperature below thermoneutral than at thermoneutral temperature, it may be supposed that the decrement in the SNS activity produced by T 4 treatment influences UCP1 expression to a lesser degree at thermoneutral than at subthermoneutral temperature. On the other hand, in BAT, T 3 has little ability, if any, of inhibiting D2 activity and even 2-fold increases are reported (Silva & Larsen 1986). Tri-iodothyronine-induced hyperthyroidism increases D2 mRNA levels (Croteau et al 1996) and cultured rat brown adipocytes require T 3 for the adrenergic stimulation of D2 mRNA expression and D2 activity (Martinez-deMena et al 2002).…”

“…Nevertheless, the action of thyroid hormones on BAT is complex and is dependent on tri-iodothyronine (T 3 ) content (Bianco & Silva 1987), a physiologically active thyroid hormone. Since T 3 concentration in BAT is strongly influenced by D2 that is inhibited by its substrate thyroxine (T 4 ) (Silva & Larsen 1986), it might be argued that BAT of T 4 -hyperthyroid rats may lack T 3 (Ablenda & Puerta 1992). Otherwise, nuclear and mitochondrial thyroid receptors in BAT of T 3 -hyperthyroid rats can be occupied fully by excessive T 3 .…”