that compensation occurs more quickly in rats because rats have a smaller reserve capacity of thyroid hormones than humans.

Another example of different responses to perchlorate is related to changes in serum concentrations of thyroid hormones and thyrotropin (thyroid-stimulating hormone, TSH). For example, Siglin et al. (2000) treated male and female rats with ammonium perchlorate at 0.01-10 mg/kg per day. At 14 days, serum T4 concentrations were significantly decreased at 10 mg/kg per day in both male and female rats. Serum T3 concentrations were significantly decreased in males at 0.01 mg/kg per day or higher. No significant decreases were observed in serum T3 concentrations at any dose in female rats. Serum TSH concentrations were significantly increased at 0.20 mg/kg per day or higher in males and at 0.05 mg/kg per day or higher in females.

Studies in adult humans have not found increases in serum TSH or decreases in serum T4 or T3 with potassium perchlorate exposure over a similar period. For example, administration of 10 mg of potassium perchlorate per day (0.1 mg/kg of perchlorate per day assuming a 70-kg human) to healthy men for 14 days resulted in no changes in serum thyroid hormone or TSH concentrations during the exposure period (Lawrence et al. 2000). Similarly, Greer et al. (2002) found no decreases in serum thyroid hormones or increases in serum TSH in healthy men and women given perchlorate at up to 0.5 mg/kg per day for 14 days.

There are important differences between rats and humans in pituitary-thyroid function during pregnancy. In humans, serum total T4 and T3 concentrations rise progressively—on the average, about 50% during the first trimester of pregnancy—and remain increased during the remainder of pregnancy (Glinoer 1997). That response is due to an increase in serum TBG, which is stimulated by an increase in estrogen production (see Chapter 2). During the first trimester, serum free T4 and T3 concentrations also increase slightly because of stimulation of the thyroid gland by chorionic gonadotropin, a hormone produced by the placenta. The primary action of chorionic gonadotropin is to sustain pregnancy, but it also has weak thyroid-stimulating activity. The increases in serum free T4 and T3 concentrations decrease TSH secretion slightly in pregnant women. Later in pregnancy, the decrease in production of chorionic gonadotropin results in a return of serum free T4, T3, and TSH to concentrations comparable with those in nonpregnant women and in men.

Thyroid hormone concentrations change during pregnancy in rats, but detailed studies are limited to gestation days 17-22. During gestation days 17-22, serum T4 concentrations in pregnant rats are significantly lower than those in nonpregnant female rats (Fukuda et al. 1980; Calvo et al. 1990;



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