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Department of Endocrinology, Metabolism, F5-165, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

(Requests for offprints should be addressed to A Boelen; Email: a.boelen{at}amc.uva.nl)

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 T₃ and T₄ and pituitary TSHß, type 2deiodinase (D2), and thyroid hormone receptor ß2 (TRß2) mRNA expression. The decrease in D2 and TRß2 mRNA expression was prevented when 20 µg leptin was administered twice during fasting. By contrast, the decrease in TSHß mRNA expression was unaffected. A single dose of leptin given after 24 h fasting did not affect decreased TSHß, D2, and TRß2 mRNA expression, while 4 h refeeding resulted in pituitary D2 and TRß2 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 TSHß, D2, and TRß2 mRNA expression, which (with the exception of TSHß) can be prevented by leptin administration during fasting. Following 24 h fasting, 4 h refeeding completely restores pituitary D2 and TRß2 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 TRß2 mRNA expression.

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