Sequential Changes in the Pituitary-Thyroid Axis during Pregnancy and Lactation in the Rat*

Dynamic changes in the pituitary-thyroid axis were studied during pregnancy and lactation by measuring plasma concentrations of TSH, T4, and T3 and the free T4 fraction (FT4F) in the rat. In contrast to human pregnancy, plasma T4 progressively decreased during the second half of pregnancy to as low as 2.6 ±0.2 /μg/dl by term compared with 6.3 ± 0.3 /μg/dl on day 0 of pregnancy (P < 0.01). Plasma T3 concentration underwent a smaller proportional decrease than plasma T4 (66.5 ± 6.2 ng/dl at day 0 vs. 44.6 ± 4.9 at term; P < 0.05). Despite the dramatic drop in T4) plasma TSH remained at normal levels until the 16th day of pregnancy, after which a slight, but significant, increase was seen. FT4F was twice as high during late pregnancy as in nonpregnant rats, but the free T4 concentration index was significantly lower. After delivery, high plasma TSH and low thyroid hormone levels persisted throughout lactation and returned to normal only after weaning. In rats whose pups were removed shortly after delivery (nonlactating), these hormones returned to the normal ranges within a few days. FT4F became normal in both lactating and nonlactating rats after delivery, but the free T4 concentration index was significantly lower in the former. There was a significant reduction of plasma T4 in sucklings when their nursing mother was thyroidectomized. However, nearly normal levels of plasma T4 were maintained in sucklings whose thyroidectomized mother was supplemented with a physiological replacement dose of T4. Our findings suggest that the decrease in the concentration of plasma thyroid hormones during pregnancy, at least in part, results from a decreased binding capacity of plasma proteins, and, in contrast, that the decrease in plasma thyroid hormone concentration during lactation probably results from a loss of thyroid hormones into milk. In rats, the relative hypothyroid state in pregnancy thus appears to be due to a different mechanism than that in lactation.