Leptin, nutrition, and the thyroid: the why, the wherefore, and the wiring.

to produce the thyroid hormones T3 and T4, which regulate gene transcription throughout the body (1). In medical practice, the thyroid becomes an issue when its size or shape becomes abnormal or when it produces too much or too little hormone. Thus, we typically think of the thyroid with reference to the clinical states of goiter, or hyper-or hypothy-roidism. But what is the physiology of the thyroid when the gland and the entire hypothalamic-pituitary-thyroid axis are intact? As first year medical students ask each year, Why exactly do we have a thyroid, at all? The usual presentation of thyroid physiology does not stress dynamic changes in hormone levels. Unlike insulin or cortisol levels, which are widely understood to fluctuate in response to food ingestion and stress, respectively, thyroid hormones are typically thought to be maintained at a basal level of hormone that keeps the metabolic machinery humming at the proper rate. In our opinion, this static view of thyroid physiology is mistaken. Nutrition and thyroid hormones. In addition to changes in thyroid hormone that occur in development, from tadpoles to mammals, thyroid hormone levels are subject to major physiologic regulation during the transition from the fed to the starved state. In the well-studied rodent model, starvation rapidly suppresses T4 and T3 levels (2, 3). The benefit of this suppression is clear: Starvation represents a severe threat to survival, and, in rodents, the capacity to survive without nutrition is measured in days. Because thyroid hormones set the basal metabolic rate, a drop in thyroid hormone levels should reduce the obligatory use of energy stores. As long as hypothyroidism does not impair the ability to obtain food, this adaptation would be expected to enhance survival. Because animals in the wild are thought to commonly experience periods of starvation, the thyroid response to starvation should be viewed as a major aspect of the regulatory biology of the thyroid gland. The thyroid system is regulated at multiple levels, one or more of which might account for nutritional adaptation. First, thyrotropin-releasing hormone , a neuropeptide produced in the paraventricular nucleus (PVN) of the hypothalamus, controls the release of thyroid-stimulating hormone (TSH) from the pituitary. TSH acts on receptors on the thyroid to promote synthesis and release of the thyroid hormones T4 and T3. In addition, a family of deio-dinases metabolize the less-active T4 to the more-active T3 or to the inactive reverse T3. In primary …