Effect of (-)-N-[(S)-hexahydro-l-methyl-2, 6-dioxo-4-pyrimidinylcarbonyl]-L-histidyl-L-prolinamide (TA-0910), a new TRH analog, on plasma levels of TSH and thyroid hormones in rats

Abstract

The stimulatory effect of TA-0910 on the secretions of thyroid-stimulating hormone (TSH) and thyroid hormones was investigated in male and female rats. Single intravenous administration of TA-0910 at 8.3 nmol/body acutely elevated the plasma TSH level, with delayed and moderate increases of T₃ and T₄ in plasma. Similar increments of plasma TSH and thyroid hormones were observed when TRH was injected at the dose of 0.83 nmol/body. Oral administration of TA-0910 at 2.75μmo1/body was equally potent or slightly more potent to secrete TSH than TRH at 0.275 μimol/body. The elevated TSH by TA-0910 decreased to the control level within 2 hr after intravenous injection or within 6 hr after oral administration; on the other hand, the higher levels of the thyroid hormones were retained for up to 4 and 6 hr after intravenous and oral administration, respectively. These findings indicate that TA-0910 and TRH stimulate the secretion of TSH and thyroid hormones by a similar manner and that the TSH-secreting activity of TA-0910 is lower by an order of magnitude compared with that of TRH.