Differential Adaptations of the Hypothalamus-Pituitary-Thyroid Axis Between Food Restriction and Anorexia

The hypothalamic-pituitary thyroid (HPT) axis plays a critical role in mediating changes in metabolism and thermogenesis. Its regulation is mainly determined by thyrotropinreleasing hormone (TRH), which is a tripeptide (pGlu-His-ProNH2) synthesized in the paraventricular nucleus (PVN) of the hypothalamus. TRH-containing-neurons of medial and periventricular parvocellular compartments of the PVN are essential for HPT axis regulation since they are the only ones with hypophysiotrophic properties (Lechan & Fekete, 2006). Axon terminals of TRHergic neurons are highly dense in the median eminence (ME), in close apposition to capillaries of the hypophysial-portal system (Toni & Lechan, 1993), where TRH is released and able to stimulate the synthesis and release of thyrotropin (TSH) and prolactin from anterior pituitary (Bowers et al., 1968; Harris et al., 1978). TSH then stimulates thyroxine (T4) and triiodothyronine (T3) synthesis in the thyroid gland as well as their release into the peripheral circulation. Under normal conditions only a small fraction of T3 is generated by the thyroid gland, the remainder of T3, which is available for binding sites in the plasma and body cells, is produced by monodeiodination of T4 (Danforth, 1983). This action is catalyzed by both type 1 (D1) or type 2 (D2) iodothyronine deiodinases, the first is abundant in liver, kidney and pituitary (Araujo et al., 2008) whereas the latter is mainly present in brown adipose tissue (BAT), pituitary and Central Nervous System (CNS) (Diano et al., 1998). The enzyme activity of the liver and kidney is responsive to the nutritional status of an organism and is found to be more active during states of accelerated glucose metabolism (Danforth, 1983).