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

Abstract

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 14 C02 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 14 C02 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-14 C 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 ...

Behavioral Testing of Progenies of Tx (Hypothyroid) and Growth Hormone-Treated Tx Rats: An Animal Model for Mental Retardation

“…We have demonstrated in previous studies that amino acid uptake and utilization in brain and brain protein and glycoprotein synthesis are impaired in the fetuses, neonates, and adult progenies of Tx mothers [16,17,20]. In fact, in some recent studies we find the extracellular to intracellular ratios of most free amino acids to be exceptionally low in the offspring of Tx mothers [unpublished observations].…”

“…This concept is in accord with that of G ina I ska -Matin o wska and Romer [15] who suggest that GH exerts its effects by altering or promoting placental develop ment. Our previous studies have, indeed, shown that many of the fetal and neonatal metabolic aberrations produced by maternal Tx are corrected by GH treatment oftheTx mother [16,17,20,32,34,35], especially amino acid supply to and protein synthesis in brain of fetuses and neonates [16,17,20]. The fact that GH treatment of the Tx mother normalizes protein-RNA synthesis and that memory is significantly improved also in the progenies of these mothers may point to one of the most important aspects of these studies.…”

“…However, as the 5-day-old and older neonates are not hypoglycemic, other mechanisms must be involved. Although food restric tion of control mothers produced no real detrimental effect per se, it may play a role in the Tx mother who has many metabolic abnormalities and does not supply the fetus with normal amounts of substrate [16,17,20], Deficiencies of single amino acids in the mother such as asparagine [29] and taurine [14] during nursing, or maternal protein deficiency pre-and postnatally [11], result in impairment of brain devel opment in the offspring just as does hyperphenylalaninemia [5] which is a well documented disorder which leads to mental retardation.…”

“…The transfer of amino acids from the Tx mothers to their fetuses is impaired [16,20] and the tissue (brain, liver) uptake of amino acids is decreased in the fetuses and 1-, 5-, 30-and 60-day-old offspring of these mothers [16. 20], The abnormal metabolism of amino acids may be only one con tributing factor, nevertheless: brain, liver, and serum protein and glycoprotein synthesis are reduced significantly in fe tuses, neonates, and adult progenies of Tx mothers [16,17,20], The administration of relatively small doses (0.5 or 1.0 IU /rat/day) of growth hormone (GH) to the Tx rat during the last 10 days of gestation reverses many of these metabolic effects of maternal Tx in their neonates and adult progenies as well as their fetuses [16,17,20,32,34,35].…”

Iodothyronine-5′-Deiodinase Activity in Progenies of Hypothyroid Rats

“…They have deficient cellular amino acid uptake and protein synthesis in brain, liver and skeletal muscle (Hendrich, Wiedmeier and Porterfield 1982;Hendrich and Porterfield 1980). At the time of birth, these pups have fewer brain and liver cells and much lower protein concentrations in these tissues (Porterfield and Hendrich 1982). Furthermore, total brain and liver RNA are low in the perinate (Porterfield and Hendrich 1982).…”