The administration of iodide to pregnant and nursing rats induces hypothyroidism in the term fetus and neonatal rat through age 10 days as indicated by an increase in the serum concentration of thyroid-stimulating hormone and a decrease in the serum of thyroxine and triiodothyronine. Thyroid function returned to normal from age 18 through 60 days in spite of continued iodide administration, strongly suggesting that resistance to the inhibitory effect of iodide on thyroid hormone synthesis is developed at approximately 18 days of age. This perinatal rat model can be used to study the mechanisms responsible for iodide-induced hypothyroidism and goiter in human newborns whose mothers received iodide-containing medications during pregnancy.
A B S T R A C T To determine the role of thyrotropinreleasing hormone (TRH) in the regulation of thyroidstimulating hormone (TSH) secretion in the perinatal period, a physiological approach of neutralizing circulating TRH in the fetal andl early neonatal rat was employed. TRH-antiserum (TRH-AS) raised in rabbits and administered daily to low iodine-propylthiouracil (LID-PTU)-fed pregnant rats from days 12 to 19 of gestation markedly impaired the rise in serum TSH to LID-PTU when compared with normal rabbit serumtreated controls. In contrast, fetal serum TSH was unaffected by TRH-AS. The binding capacity of TRH-AS in the fetal serum (111 ng/iiil) far exceeded circulating TRH in the fetus. Similarly7, acute TRH-AS administration to the pregnant rat fed LID-PTU markedly decreased the serum TSH concentration in the mother, but not in the fetus, 60 niin after TRH-AS administration. Chronic TRH-AS administration to neonatal rats whose nursing mothers were fed LID-PTU was ineffective in decreasing the elevated serum TSH in the neonate through day 8 of life, whereas a slight but significant decrease in serum TSH was observed on day 10. Chronic daily TRH-AS administration to neonatal rats through day 10 of life had no effect on the later development of the hypothalamic-pituitary-thyroid axis. These findings suggest that TRH does not participate in TSH regulation during the perinatal life in the rat and that thyroid hormones are probably the main regulators of TSH secretion during this period.Placental TRH is niot importanit in regulating TSH secretion in the fetal rat. Furthermore, TRtH "deprivation" during neonatal life does not prevent normal later developmenit of the hypothalamic-pituitarythyroid axis.
Chronic diphenylhydantoin (DPH) administration (5 mg x 100 g body wt-1 x day-1) to the normal rat is associated with a decrease in the serum thyroxine (T4) and triiodothyronine (T3) concentrations without an appropriate rise in the serum thyrotropin (TSH) concentration, suggesting a possible direct effect of DPH on TSH secretion. To further study this possibility, DPH was administered chronically to thyroidectomized, hypothyroid rats. In the hypothyroid rats treated chronically with DPH, serum TSH did not increase, pituitary TSH content was significantly decreased, and the serum TSH response to thyrotropin-releasing hormone (TRH) was decreased compared to that of diluent-treated, hypothyroid rats. Hypothalamic TRH content was similar in DPH and diluent-treated rats. These findings suggest that DPH suppresses pituitary TSH secretion, probably as a thyroid hormone agonist. The effect of a single large dose of DPH (20 mg/100 g body wt) administered to thyroidectomized rats also decreased serum tSH but, in contrast to the findings in chronically treated rats, hypothalamic TRH and pituitary TSH content and the serum TSH responses to TRH were increased. These differences may be due to the acute inhibitory effect of a large dose of DPH on hypothalamic TRH release. Furthermore, because the effect of thyroid hormone on regulating pituitary TSH synthesis and release is dose and time dependent, the effect of DPH as a thyroid hormone agonist on pituitary TSH dynamics may also be variable.
The ultrastructure of Alzheimer's neurofibrillary tangles is heterogeneous and includes abnormal paired helical filaments (PHF) and various other insoluble structures. Insoluble non-PHF components isolated from neurofibrillary tangles were examined by electron microscopy. Comparison of these fractions with normal assembled neurofilaments and normal brain microtubules revealed scattered profiles which were morphologically (not chemically) identical to structures present in the microtubule, but not in the neurofilament preparations. These results support the notion that insoluble microtubules contribute to the make up of the neurofibrillary tangle. Based on these findings, preliminary experiments were conducted which suggest that non-enzymatic glycosylation may be a pathway leading to insolubility of the microtubules.
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