Thyroid Hormone Regulation of Hypothalamic Immunoreactive Thyrotropin*

Immunoreactive TSH (IR-TSH) has been identified in the hypothalamus and other brain areas in intact and hypophysectomized rats. To determine if thyroid hormones regulate IR-TSH in the rat brain, the effects of T3 and T4 on pituitary and hypothalamic IR-TSH content were studied in intact and hypophysectomized rats. Female rats received daily injections of T3 (0.1, 1.0, or 10 micrograms/100 g BW) or T4 (0.5, 2.5, or 5.0 micrograms/100 g BW) for 7 days. The chronic administration of T3 and T4 decreased the plasma concentration and pituitary content of IR-TSH in a dose-dependent manner. In intact rats, the administration of T3 did not affect the content of IR-TSH in the median eminence, ventral hypothalamus, or dorsal hypothalamus. In contrast, administration of T4 significantly increased the content of IR-TSH in the median eminence and ventral hypothalamus in a dose-dependent manner. Similarly, in hypophysectomized rats daily administration of T4 resulted in a dose-dependent increase in the concentration of IR-TSH in the median eminence and ventral hypothalamus. In hypophysectomized rats infusion of colchicine into the lateral ventricle, which blocks axonal transport, decreased the content of IR-TSH in the median eminence (631 +/- 59 vs. 439 +/- 36 microU/mg), increased the content of IR-TSH in the ventral hypothalamus (45 +/- 5 vs. 87 +/- 10 microU/mg), and blocked the T4-induced increase in IR-TSH in the median eminence. In intact rats, administration of iopanoic acid, which blocks the conversion of T4 to T3, decreased the content of IR-TSH in the median eminence (688 +/- 44 vs. 450 +/- 38 microU/mg) and ventral hypothalamus (103 +/- 16 vs. 70 +/- 5 microU/mg) and blocked the T4-induced increase in IR-TSH in the median eminence (1025 +/- 82 vs. 644 +/- 62 microU/mg) and ventral hypothalamus (229 +/- 23 vs. 117 +/- 11 microU/mg). These data indicate that TSH content in the median eminence and ventral hypothalamus is regulated by a thyroid hormone-sensitive mechanism which requires the local monodeiodination of T4 to T3. In addition, the effect of colchicine on the IR-TSH content in the median eminence and the T4-induced increase in brain IR-TSH are consistent with previous reports demonstrating that hypothalamic IR-TSH is regulated independently of pituitary and serum TSH.