Thyrotropin‐releasing hormone has stimulatory effects on ventilation in humans

Abstract

Thyrotropin-releasing hormone (TRH) stimulates pituitary thyrotropin synthesis and release and also regulates autonomic nervous system functions by acting as a neuromodulator and neurotransmitter. In experimental animals a stimulation of ventilation by thyrotropin-releasing hormone was shown when applied at central nervous system sites that affect respiratory motor output. It was the goal of our study to investigate the respiratory properties of thyrotropin-releasing hormone on basal and stimulated (i.e. CO2-rebreathing) conditions following systemic thyrotropin-releasing hormone application in healthy humans. Thyrotropin-releasing hormone (200 micrograms, 400 micrograms intravenous) initiated a rapid short lasting rise of minute volume, ventilatory air-flow and alveolar oxygen tension under steady state breathing (P less than 0.001). Breathing frequency was less affected, heart rate rose concomitantly (P less than 0.001). While breathing with increasing concentrations of carbon dioxide, minute volume was higher under thyrotropin-releasing hormone than under placebo alone. Further effects (e.g. nausea, dizziness, palpitations) mostly appeared later than respiratory changes and thus may not be responsible for their initiation. Our findings prove systemic thyrotropin-releasing hormone to be a strong respiratory stimulant in man. Response in respiratory output was also accompanied by central nervous system-effects (e.g. dizziness, restlessness, augmented vigilance). The mode of thyrotropin-releasing hormone effects on respiration after peripheral administration is still speculative. An augmented sympathetic output or a direct receptor mediated action at central nervous system sites may be responsible, while a peripheral effect cannot be excluded.

Serotonin Neurons and Central Respiratory Chemoreception

“…Conversely, PCPA, PCA and 6-FT deplete 5-HT, but the neurons remain intact and would continue to release TRH and SP. The decrease in extracellular 5-HT levels would lead to loss of 5-HT 1A receptor-mediated autoinhibition, which could increase release of TRH and SP, both of which have powerful stimulatory effects on breathing (Yamamoto et al 1981, Hedner et al 1983, Nink et al 1991). The end result of 5-HT depletion might be greater stimulation of the respiratory network rather than less.…”

RNASeq‐derived transcriptome comparisons reveal neuromodulatory deficiency in the CO2 insensitive brown Norway rat

“…Finally, although thyroid dysfunction has been linked to reduced CO 2 sensitivity in humans, TRH infusions in healthy humans have no effect on the CO 2 chemoreflex (Nink et al . ; Schulz et al . ).…”

The pre-Bötzinger complex participates in generating the respiratory effects of thyroliberin

“…To a great extent this is because the pronounced stimulatory effect of thyroliberin on respiration in mammals and humans [17][18][19]23, 29] provides a basis for the future use of thyroliberin analogs in clinical medicine. The question of the CNS structures mediating the respiratory effects of thyroliberin is of special interest, as is that of the physiological mechanisms underlying these effects.…”