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 ...

Iodothyronine-5'-deiodinase activity (I-5'DA) was measured in the progenies of control rats, hypothyroid (Tx) rats, and hypothyroid treated with ovine GH (Tx + GH) during gestation. The enzyme was measured in cerebral cortex and cerebellum at 22 days gestation and at 5, 10, 30 and 60 days postpartum. In addition, the pituitary I-5'-DA was assessed in the postnatal animals. The experiments were undertaken because the tissues of the progenies of rats that were hypothyroid during pregnancy appeared in many ways to resemble those of hypothyroid animals, even at ages when serum thyroxine (T4) and triiodothyronine (T3) levels were normal. It was found that the progenies of Tx mothers had low liver 5'-deiodinase activities. This is a likely cause of the low serum T3 levels with normal T4 levels seen in these progenies in the neonatal period. Cerebral and cerebellar 5'-deiodinase activities were low in these progenies during the thyroid hormone-dependent perinated period of brain development. The progenies of GH-treated Tx dams had higher enzyme activities than the progenies of untreated Tx dams. These pups from GH-treated Tx mothers have been shown previously to have significantly less neurological impairment than the progenies of untreated Tx mothers. As most of the brain intracellular T3 is produced in situ, a functional thyroid deficiency could result from such a 5'-deiodinase deficiency. As the deiodinase deficiency was still seen in the progenies of Tx mothers at 60 days of age, such a deficiency could explain why, even though serum T4 and T3 levels were normal, brain metabolism was in many ways characteristic of hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Rats (200-260 g) were exposed in sealed, recycling chambers continuously for 2-30 days to gas mixtures designed to maintain the same alveolar PO2 in the presence or absence of inert gas. Mixtures with inert gas (N2, He, or Ne) were at ground level; those without inert gas (100 percent O2) were in an altitude chamber. The O2 categories were: I-100 percent O2 at 747 torr; II-74 percent O2 + 26 percent inert and 566 torr 100 percent O2; III-47 percent O2 + 53 percent inert and 381 torr 100 percent O2; IV-21 percent O2 + 79 percent inert and 197 torr 100 percent O2. One of the two room-air controls was "restricted-fed" to the level of the lowest intake group. Measurements included body, pituitary, and thyroid weight, food and water intake, plasma volume and hematocrit, pituitary and plasma TSH, and plasma PBI. Severe depression in all variables and over 50 percent mortality was seen in I by day 4. All variables were depressed in II, but there was no mortality to 20 days. Pituitary-thyroid function appeared to be particularly sensitive to depression by hyperoxia, with plasma TSH levels reduced between 42 and 60 percent in II and III. No effect was attributable to the inert gas, whether it was N2, He, or Ne, nor was any specific effect traceable to the presence or absence of inert gas.