S tarvation in laboratory rodents results in significant alterations in thyroid hormone economy characterized by decreased circulating levels of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) and a decline in serum thyrotropin (TSH) concentration. To investigate this apparent paradox, we have compared in fasted and hypothyroid animals the intracellular parameters mediating thyroid hormone action in the anterior pituitary gland. In vitro saturation analysis combined with quantitation of nuclear T3 content by radioimmunoassay allowed for characterization of pituitary nuclear T3 receptors and estimation of the endogenous fractional receptor occupancy. In rats, thyroidectomized 4 wk earlier, the 10-fold increase in serum TSH levels and decline in peripheral thyroid hormone concentrations were accompanied by a 61% decrease in pituitary nuclear T3 content and a marked decline in fractional T3 receptor occupancy as compared with control animals. In euthyroid animals subjected to short-term starvation (72 h), serum T3, T4, and TSH levels declined by 52, 43, and 48%, respectively. Despite these marked decreases in circulating thyroid hormone levels, pituitary nuclear T3 content in fasted rats declined by only 15% (P less than 0.05) relative to control levels. This modest decline in nuclear T3 content, combined with a 23% decrease in total T3 receptor number, resulted in an estimated fractional receptor occupancy in fasted animals which was equal to or greater than that noted in controls. The effects of fasting and hypothyroidism on the pituitary were further investigated by quantifying low Michaelis constant (Km) T4 5'-deiodinase activity in the crude cytosol fraction of pituitary homogenates. In thyroidectomized animals, maximum velocity was increased ninefold, whereas fasting resulted in a 37% decrease (P less than 0.025) in this parameter compared with controls. Km values were similar in all experimental groups (4.7 +/- 0.6 nM). These results demonstrate that, despite significant reductions in circulating thyroid hormone concentrations and pituitary T4 5'-deiodinase activity, nuclear T3 levels are maintained at relatively normal levels in the pituitary of the fasted animal and fractional T3 receptor occupancy may actually increase. These findings are in marked contrast to those noted in thyroidectomized animals and suggest that the suppression of TSH secretion accompanying starvation in the rat is mediated, at least in part, by local pituitary mechanisms that serve to maintain and possibly enhance nuclear T3 receptor occupancy.