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A B S T R A C T We studied the effect of thyroid hormone administration on responsivity of murine thyroid to exogenous thyrotropin (TSH) in order to explore the possibility that the thyroid gland might be directly inhibited by its own hormones. In the rat both L-thyroxine (T4) and 3,5,3'-L-triiodothyronine (T3) pretreatment inhibited TSH-induced thyroidal ornithine decarboxylase (ODC) activity in vivo in a dose-related manner (half-maximal inhibition, 1.7 /Ag/rat and 0.6 /Lg/rat, respectively). Other structurally related compounds exhibited the following inhibitory potencies compared to T4: T3, 283%; triiodothyroacetic acid, 40%; D-T4, 18%; 3,5-L-diiodothyronine, 9%. Monoiodotyrosine, diiodotyrosine, and iodide were not inhibitory. The full inhibitory effect of T4 or T3 was observed when thyroid hormone was administered from 96 to 12 h before TSH and was also seen in hypophysectomized animals. Pretreatment with T4 or T3 in divided doses over 2i days inhibited TSH-induced increase in [1-14C]glucose oxidation to 14CO2 and [3H]leucine incorporation into protein in rat thyroid.In the mouse T4 or T3 pretreatment (0.25-25 Ag daily) caused dose-related inhibition of both thyroidal ODC activity and "31I release induced by TSH in vivo.In mice on a low-iodine diet (LID) but not in animals on a regular diet (RD) NaI pretreatment also blunted TSH-induced thyroidal ODC activation and "'I release. When LID or RD mice were pretreated with 12.5-125 ,ug of T4 or T3 over 2i days, TSH-induced in vitro stimulation of thyroid cyclic 3',5'-adenosine monophosphate formation was inhibited in a dose-related manner; NaI pretreatment was inhibitory in the LID mouse only. Prior administration of exogenous TSH blunted the activation of thyroid ODC and thyroid hormone release induced by subsequent TSH administration in rat and mouse. These studies indicate altered thyroid responsivity to TSH under the influence of circulating thyroid hormones and suggest the existence of a "short-loop" negative feedback regulating thyroid function. INTRODUCTIONThe results of recent studies (1, 2) suggest that an increase in circulating thyroid hormone levels may impair thyroidal responsivity to exogenous thyrotropin (TSH).' It was therefore felt to be of interest to explore this possibility further by studying the effect of thyroid hormone administration on TSH-augmented thyroid function in the rat and mouse. The results indicate that such treatment does, in fact, occasion decreased thyroid gland response to exogenous TSH and suggest the existence of a "short-loop" negative feedback regulating thyroid function.

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A sulphamidase activity present in rat spleen capable of hydrolysing N-[(35)S]sulphated heparin was studied. This activity was associated with the lysosomal fraction. Studies in vivo showed that the rat is capable of significantly desulphating heparin. Lysosomes in all the major tissues can effectively accumulate heparin. The heparin sulphamidase and arylsulphatase activities from rat spleen were separated by isoelectric focusing. Heparin sulphamidase was a distinct entity from all the arylsulphatase activities.