Effects of Continuous and Pulsatile Administration of Pituitary Rat Thyrotropin and Recombinant Human Thyrotropin in a Chronically Cannulated Rat

Pulsatile secretion of thyrotropin (TSH) is a well characterized phenomenon in the human, yet only limited data are available from animal studies. We propose a combined model of chronic catheterization and suppression of endogenous TSH release in the rat allowing us to apply quantified pulses of different preparations of thyrotropin intravenously with minimal interference with endogenously produced hormone. Sprague-Dawley rats treated with drinking water containing 3,5,3′-triiodothyronine (T3) showed a significant 6-fold decrease of the rat TSH (rTSH) level after four days. Free thyroxine (FT4) levels were 9-fold below unsuppressed levels; FT4 response to exogenous TSH application above this suppressed baseline level was selected as an endpoint. Infusion studies compared pulsatile with continuous TSH administration. A low and a high dose of rTSH and recombinant human TSH (rec-hTSH) were administered. Levels of FT4 were compared after two and four days and responsiveness to a standard high bolus of rTSH 6 h after end of infusion was assessed. With regard to its potency for FT4 release, differences indicating a general trend as to superior efficiency of pulsatile TSH stimulation of the thyroid gland in comparison to continuous stimulation could be observed in all four experiments. More pronounced effects were seen after 2 and 4 days of high rTSH infusion and after 4 days of low rec-hTSH infusion. Comparison of FT4 responses to rTSH boli showed a 2- and 6-fold higher response in the pulsatile group compared to the continuous group after low and high rTSH infusion, respectively. This was not observed in the animals receiving low rec-hTSH infusion. However, after high rec-hTSH infusion, a bolus following pulsatile infusion resulted in a lesser decrease in FT4 levels in comparison to that after continuous application. Our data suggest that pulsatile application of TSH might be of superior efficiency with regard to in vivo stimulation of thyroid hormone secretion, hence suggesting an underlying physiological significance of this release pattern.