may impair the ability of iron-deficient animals to produce heat from shivering. The decrease in mitochondrial enzymes that results from iron deficiency may not be a significant factor, however, in limiting the heat production in iron-deficient rats. This is suggested by the observation that iron-deficient rats injected with pharmacological doses of norepinephrine are able to attain metabolic rates that are even higher than those of noniron-deficient control rats given the same dose of norepinephrine (Tobin and Beard, 1990).
Iron-deficient anemic rats rapidly become hypothermic when placed in a cold environment (39°F [4°C]), and correcting their anemia by infusing them with red blood cells restores their thermoregulatory performance (Beard et al., 1984). Likewise, poor cold responses were induced in control rats by transfusion to a lower hematocrit level. Correcting anemia also improved thyroid response to cold. Whereas cold-exposed, anemic, iron-deficient rats did not increase their plasma T3 and thyroid-stimulating hormone (TSH) levels, correction of the anemia by transfusion resulted in a normal thyroid response to cold exposure (increased plasma T3 and TSH concentrations). Not all iron-deficiency-induced alterations are reversible by correction of anemia. After an increase in the hematocrit levels of iron-deficient rats, plasma norepinephrine concentrations remained elevated (Dillmann et al., 1979), and the norepinephrine content of heart and brown adipose tissue remained depressed (Beard et al., 1990b) compared to control rats with similar hematocrit values.
Much of thermoregulation is ultimately controlled by central neural control of blood flow, heat production, and heat loss. Thus, the impact of micronutrient deficiency states on temperature regulation can often be traced to control of neurohormone production (Brigham and Beard, in press).
There is also evidence that iron deficiency may alter neurohormonal control of thermoregulation centers in the central nervous system by way of an effect on dopamine, serotonin, and norepinephrine. The brains of iron-deficient rats were observed to contain excessive quantities of dopamine in the caudate-putamen region, and the number of D2 receptors in the brain was lowered by iron deficiency (Youdim et al., 1989). Beard and coworkers have recently extended these observations and determined, through the use of in vivo microdialysis, that extracellular dopamine is elevated in awake, freely moving animals who were made iron deficient by dietary means only (Beard et al., 1994). Thus, the down regulation of dopamine receptors by iron deficiency may be the result of a direct effect of iron on receptor biology or may be the result of elevated extracellular-fluid dopamine concentrations. This latter observation is consistent with evidence that dopamine-dependent circadian cycles are reversed in iron-deficient rats (Youdim and Yehuda, 1985), although others have not verified the circadian cycle effect (Hunt et al.,