Effect of N3im-Methyl-Thyrotropin Releasing Hormone on the Human Pituitary-Thyroid Axis

Abstract

The N^3im-methyl analogue of thyrotropin release hormone (methyl-TRH) was compared with TRH as a thyrotropin releaser in 30 euthyroid volunteers (ages 19–61 years)The mean TSH response to 100 μg of methyl-TRH was greater (P < 0.005) than the TSH response to 500 μg of TRH from 10 min to 240 min after giving the releasing factors. The mean peak TSH (at 30 min), maximum ΔTSH, and integrated TSH response area were greater (P < 0.005) after administration of methyl- TRH than after TRH. The TSH response tomethyl- TRH was significantly greater (P < 0.05) for the 11 females than for the 19 males in this study. The mean baseline TSH was correlated with the maximum ΔTSH (r= 0.72, P < 0.01) after methyl-TRH stimulation. The mean serum T₃ concentration after methyl-TRH was significantly elevated at 60 min, peaked at 210 min and remained significantly elevated at 240 min. The peak serum T₃, maximum T₃ and T₃ response area were significantly greater (P < 0.005) after givingmethyl-TRH than after TRH. The methyl-TRH induced T₃ response area was 1.4 times the TRH induced T₃ response area. The serum T₄ concentration after methyl-TRH was elevated at 90 min (P < 0.005), reached a peak at 210 min, and at 240 min wasstill 125 times the mean baseline T₄. The peak serum T₄, maximum ΔT₄ and T₄ response area after methyl-TRH were significantly greater than after TRH. The methyl-TRH induced T₄ response area was 1.4 times the TRH induced T₄response area. The data indicate that methyl-TRH is a more potent thyrotropin releaser than TRHSince N^3im-methylhistidine has been found in the brain, the possibility that this methyl analogue of TRH is a physiologic thyrotropin releaser should be evaluated.