Age-dependent extinction of thyrotropin-releasing hormone in the human cerebellum

Immunoreactive TRH was quantified in eight regions of the cerebellum as well as in the medulla, pons, and hypothalamus of the fetal and adult human brain. High levels of TRH were detected in the fetal cerebellum, ranging from 216 +/- 103 pg/mg protein (mean +/- SD) in the deep cerebellar nuclei to 591 +/- 153 pg/mg protein in the anterior vermis. The concentrations of TRH were significantly greater (P less than 0.001) in each of the eight regions of the cerebellum of the fetal brain than in the corresponding regions of the adult brain. The magnitude of the difference between adult and fetal cerebellar levels ranged from an 18-fold difference in the deep cerebellar nuclei to more than a 100-fold difference in the anterior hemisphere. However, the TRH levels in pons and medulla were similar among fetuses and adults, and the TRH concentration in the adult hypothalamus was significantly higher (P less than 0.01) than that in the fetal hypothalamus. The TRH levels in adult rat hypothalami were extremely stable for several hours post mortem. We, therefore, conclude that the differences in cerebellar TRH concentrations of the fetal compared to those of the adult human are not related to a difference in the extent of postmortem degradation of TRH. Rather, we postulate that the decline in cerebellar TRH during maturation is a normal developmental process, and speculate that TRH, which has been found to have diverse effects on the central nervous system, may also influence the development of the human cerebellum.