Tissue metabolism of thyroid hormones in hypothyroid and growth hormone treated hypothyroid mothers, their fetuses and their progenies

Abstract

Studies of Man et al. have shown that the children of hypothyroxinemic women have an .increased rate of mental and .motor retardation. A rat model which presents the ~etabolic and motor defects of these children developed by Hendrich et al. was used for these studies. The metabolism of T4 was studied i~ the progenies of Tx-only and GH-treated Tx dams utilizing a radioimmunoassay for T4 detection and equations based on those of Inglebleek .~d Malvaux. In the above mentioned study, the hypothyroid dams showed an impaired reproductive performance that included lower body weight gain, smaller liter size and greater mortality for their pups. Furthermore, maternal hypothyroidism had a detrimental effect on their offsprings body and tissue weights. The parameters of metabolism for T4 showed that the offsprings of hypothyroid mothers have a clear derangement in the utilization of this hormone at the ages studied (i.e., 5, 30, 60 days of age). The next step in our investigation wa~ to measure the iodothyronine concentrations intracellularly to determine how these J molecules were utilized. We developed a new technique for the extraction of iodothyronines based on HPLC fluorescence. The extracted iodothyronines were derivatized with dansyl chloride and then rap in our chromatographic system. The iodothyronine concentrations ·in the tissues {i.e., brain and liver) and plasma for the progenies of hypothyroid mothers at all ages {i.e,. 22 day, 10, 30, 60 day-olds} were consistently abnormal confirming what we saw with the metabolic studies of T4 done initially. The hypothyroid mothers had iodothyronine concentrations consistently abnormal in all tissues studies. The progenies of hypothyroid mothers appear to suffer an insult that causes a severe impairment in the metabolism of T4. This insult not only affects the metabolism of T4 but also affects the concentrations' of other iodothyronines in liver, brain and plasma