Utilization of Alanine by Hypothyroid and Growth Hormone Treated Hypothyroid Rats, their Fetuses and Progeny

Summary

Maternal thyroidectomy (Tx) results in decreased maternal and fetal liver glycogen and protein as well as fetal serum glucose and maternal and fetal serum protein on the 22nd day of gestation. Progeny of Tx mothers continue to show reduced serum and liver protein levels at 1, 5 and 30 days of age. Their serum glucose is also depressed at 1 and 5 days of age but is elevated over that of control progeny by 30 days of age; whereas, liver glycogen is elevated at 1 day of age but is similar to control progeny at 5 and 30 days of age. Growth hormone (GH) treatment of the Tx mother generally reverses these effects but does not correct reproductive performance of the Tx rat. These data on maternal and fetal tissue levels of glucose and glycogen confirm our previous observations.

Alanine plays a major role in glucose as well as protein homeostasis. The utilization of alanine-U-¹⁴C was assessed by determining the amount converted to glucose-glycogen, the amount incorporated into protein, the serum and liver total alanine pool, the specific activity of the liver alanine pool and in 22 day pregnant rats, the amount of ¹⁴CO₂ given off during the 30, 60 and 120 minute intervals. Maternal Tx depressed significantly the labeling of glycogen and protein in both maternal and fetal liver and reduced also the total ¹⁴CO₂ formed. Surprisingly this effect was still present for the labeling of liver protein in 1, 5 and 30 day old progeny of Tx mothers. However, the labeling of liver glycogen was increased significantly in 1 day old progeny but was similar to control progeny in 5 and 30 day olds. The maternal serum alanine of Tx-GH treated rats was reduced significantly; whereas, the fetal serum alanine of Tx only rats was decreased significantly. This was true also for the 1 and 5 day old progeny of Tx mothers. However, by 30 days of age the progeny of Tx mothers had elevated serum and reduced liver alanine levels. The rate of uptake of alanine-U-¹⁴C was depressed in the livers of the Tx mothers, their fetuses and 1, 5 and 30 day old progeny. This resulted in an early (30 min) depression of the specific activity of their liver alanine pool and a late (60 or 120 min) elevation of the specific activity of their liver free alanine pool.

GH-treatment of the Tx mother reversed these effects and labeled liver protein in fetuses and 1, 5 and 30 day old progeny was normal as was the rate of accumulation of labeled alanine in the liver and, therefore, the specific activity of the liver free alanine pool. However, liver glycogen labeling was increased 360% above controls in 22 day fetuses, remained elevated at 1 day but returned to normal at 5 and 30 days of age. The labeling of liver glycogen was essentially equal to the labeling of protein in these fetuses.

It is concluded that maternal Tx results in long term metabolic alterations in their progeny and that this effect is at least in part due to the accompanying deficiency of GH secretion in the mothers. GH appears to stimulate increased gluconeogenesis and increased utilization of available alanine in the Tx rat and her fetuses, in part, by maintaining a normal or elevated rate of uptake of alanine by tissues; whereas, the uptake of alanine from serum as well as its incorporation into protein is permanently impaired in the progeny of Tx only mothers.

Key-Words:

Maternal - Fetal - Hypothyroid - Growth Hormone - Alanine - Glycogen - Protein - Gluconeogenesis