Effects of chronic thyroid hormone administration on pregnancy, lactogenesis and lactation in the rat

We studied the effects of daily administration of 1 mg/kg thyroxine (T₄) starting 10-15 days before mating, on parturition, maternal behavior and lactation in rats. Treated rats had elevated serum titers of T₃ and T₄, a greater number of fetuses and parturition was advanced approximately 12 h and lasted longer than in controls. None of the treated rats were able to lactate because of defects in maternal behavior and milk ejection; the litters died usually within 48 h postpartum. In rats sacrificed at 10.00 on day 21 of pregnancy, mammary gland content of total protein, phospholipids, casein and lactose were significantly increased, but total lipid was markedly reduced. Lipogenesis was also significantly increased, as well as the activity of the lipogenic enzymes glucose-6-phosphate dehydrogenase, fatty acid synthetase and isocytrate dehydrogenase. These results are indicative of normal albeit premature lactogenesis. The T₄-treated rats also had advances in the prepartum fall in serum progesterone and the increase in prolactin as well as in the increase in mammary casein and lactose concentrations of approximately 12 h with respect to control pregnant rats. These results show that chronic T₄ treatment induces an advance of approximately 12 h in luteolysis, which in turn advances lactogenesis and parturition in rats. Although the mammary gland was able to produce milk, lactation failed due to abnormal maternal behavior and milk ejection, the causes of which are still unknown. Other effects of hyperthyroidism were also present, such as a severe reduction in lipid content of the gland. The observed increases in lipogenesis and lipogenic enzyme activities could be due to a combination of the effects of hyperthyoidism per se as well as to the increase in lipogenesis that occurs during lactogenesis.