A TRH-degrading ectoenzyme (TRH-DE or pyroglutamyl peptidase II) present in the membrane of tanycytes may inactivate TRH before it enters the portal vessels; TRH-DE activity is regulated in several in vivo situations such as fasting and hyperthyroidism and may be considered a modulator of the quantity of TRH that reaches the anterior pituitary (10, 11). This evidence concerns the gene TRH and hyperthyroidism.