Differential effects of leptin and refeeding on the fasting-induced decrease of pituitary type 2 deiodinase and thyroid hormone receptor β2 mRNA expression in mice

Profound changes in thyroid hormone metabolism occur in the central part of the hypothalamus-pituitary-thyroid (HPT) axis during fasting. Hypothalamic changes are partly reversed by leptin administration, which decreases during fasting. It is unknown to what extent leptin affects the HPT axis at the level of the pituitary. We, therefore, studied fasting-induced alterations in pituitary thyroid hormone metabolism, as well as effects of leptin administration on these changes. Because refeeding rapidly increased serum leptin, the same parameters were studied after fasting followed by refeeding. Fasting for 24 h decreased serum T-3 and T-4 and pituitary TSHP, type 2 deiodinase (D2), and thyroid hormone receptor beta 2 (Tk beta 2) mRNA expression. The decrease in D2 and TR beta 2 mRNA expression was prevented when 20 mu g leptin was administered twice during fasting. By contrast, the decrease in TSH beta mRNA expression was unaffected. A single dose of leptin given after 24 h fasting did not affect decreased TSHP, D2, and TR beta 2 mRNA expression, while 4 h refeeding resulted in pituitary D2 and TR beta 2 mRNA expression as observed in control mice. Serum leptin, T3, and T4 after refeeding were similar compared with leptin administration. We conclude that fasting decreases pituitary TSHP, D2, and TR beta 2 mRNA expression, which (with the exception of TSH beta) can be prevented by leptin administration during fasting. Following 24 h fasting, 4 h refeeding completely restores pituitary D2 and TR beta 2 mRNA expression, while a single leptin dose is ineffective. This indicates that other postingestion signals may be necessary to modulate rapidly the fasting-induced decrease in pituitary D2 and TR beta 2 mRNA expression.