Transient Neonatal Hyperthyroidism Results in Hypothyroidism in the Adult Rat*

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Abstract
Adult rats who had neonatal hyperthyroidism (NH) have reduced BW and serum T4, T3, and TSH concentrations. Pituitary TSH responses to TRH administration under basal, T4-suppressed, and propylthiouracil-stimulated conditions suggest that the thyrotroph of these animals is more sensitive to the feedback effects of thyroid hormones. These studies were undertaken to examine, with the use of various thyroid hormone-responsive variables, thyroid status of adult NH rats. NH was induced by 12 daily sc injections of T4 (0.4 μg/g BW) to neonatal male Sprague-Dawley rats. Adult NH and control rats were then studied at 120 days of age. Adult NH rats had significantly decreased mean BW (P < 0.001), and serum T4 (P < 0.005), T3 (P < 0.001), and TSH (P < 0.001) concentrations. The percent decreases were 12% for T4) 20% for T3, and 27% for TSH in adult NH rats. Mean pituitary GH concentration and hepatic α-glycerophosphate dehydrogenase and malic enzyme activities were significantly decreased in adult NH rats to 54% (P < 0.005), 52% (P < 0.025), and 39% (P < 0.001), respectively, of control values. Mean pituitary TSH concentrations were similar in adult NH and control rats. Mean hepatic T4 5′-deiodinase activity of adult NH rats [200 ± (SE) 23 fmol T3/min-mg protein] was significantly decreased to 56% of control levels (355 ± 31 fmol T3/min-mg protein; P < 0.005). Mean pituitary T4 5′-deiodinase activity of adult NH rats (32.8 ± 3.3 fmol T3/min-mg protein) was significantly increased compared with that of control rats (21.2 ± 1.7 fmol T3/min·mg protein; P < 0.025). These changes are consistent with a hypothyroid state in adult NH rats. The observation of decreased serum TSH concentration and enhanced thyrotroph sensitivity to thyroid hormones in the face of increased pituitary T4 5′-deiodinase activity suggests that increased thyrotroph monodeiodination of T4 may be the central biochemical aberration responsible for the hypothyroid state in adult NH rats. (Endocrinology 116: 2246–2250, 1985)