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Thyroid Hormone Regulation of Hypothalamic Immunoreactive Thyrotropin^*

WILLIAM J. DEVITO

Division of Endocrinology, University of Massachusetts Medical School Worcester, Massachusetts, 01655

Abstract

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 µg/100 g BW) or T₄ (0.5, 2.5, or 5.0 µg/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 µU/mg), increased the content of IR-TSH in the ventral hypothalamus (45 ± 5 vs. 87 ± 10 µU/mg), and blocked the T₄-induced increase in IRTSH 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 µU/mg) and ventral hypothalamus (103 ± 16 vs. 70 ± 5 µU/mg) and blocked the T₄-induced increase in IR-TSH in the median eminence (1025 ± 82 vs. 644 ± 62 µU/mg) and ventral hypothalamus (229 ± 23 vs. 117 ± 11 µU/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.

Footnotes

^* A preliminary report was presented at the 63rd Annual Meeting of the American Thyroid Association, 1988. This work was supported in part by USPHS Grant DK-32520 to the Diabetes-Endocrine Research Center (Worcester, MA) and USPHS Grant NS-26343.

To whom requests for reprints should be addressed.

Received March 17, 1989.