Triiodothyronine-induced hyperthyroidism and reproduction in female rats

The effect of L-triiodothyronine (L-T3)-induced hyperthyroidism on reproduction in female rats was studied. Treatment groups used were normal control, 1, 2, 4, 8, and 16 micrograms L-T3/100 g body weight (b.w.)/day. Subcutaneous injections of L-T3 began the first day of estrus until day 1 or day 19 of lactation. All rats given 1, 2, or 4 micrograms L-T3 had regular estrous cycles and normal number of pregnancies. Levels of L-T3 at 8 or 16 micrograms results in abnormal estrous cycles. Only one pregnancy occurred in the 8 micrograms group and no rats became pregnant in the 16 micrograms group. While groups on 1 or 2 micrograms L-T3 had normal parturition, groups on 4 micrograms or more showed signs of dystocia. Only the 1 microgram L-T3 group lactated to day 20, but at 67% of normal control. All levels above 1 micrograms showed loss of pups by day 2 of lactation due to lack of milk production, loss of maternal behavior, and cannibalism. Mammary gland wet and dried fat-free tissue (DFFT) weights were decreased in all treated groups except 1 microgram L-T3. The wet and DFFT weights of thyroids and uteri on days 2 or 20 of lactation were not altered by L-T3 treatment, but levels above 1 microgram increased both wet and DFFT weights of adrenal glands and ovaries. The data indicate that the no observed adverse effect level (NOAEL) of L-T3 for female rat reproduction would be below 1 microgram/100 g b.w./day. L-T3 treatment at 1 microgram/100 b.w./day or above is detrimental. These effects may be mediated through a hormonal imbalance due to the accelerated metabolic rate in reproductive tissues associated with hyperthyroidism.