Hormones and cerebellar development

Abstract

Cerebellar development involves various epigenetic processes that activate specific genes at different time points. The epigenetic influences include humoral influences from endocrine cells. Among circulating hormones, a group of small lipophilic hormones such as steroids (corticosteroids, progesterone, androgens, and estrogens) and thyroid hormone may particularly serve an important role in mediating environmental influences to the cerebellum. Receptors for such lipophilic hormones are mainly located in the cell nucleus (nuclear receptor, NR), and represent the largest family of ligand-regulated transcription factors. In the cerebellum, these are expressed in a specific temporal and spatial pattern. Among lipophilic hormones, involvement of thyroid hormone and gonadal steroids on cerebellar development has been well studied. Deficiency of thyroid hormone during postnatal development results in abnormal cerebellar morphogenesis in rodents. Estrogen and progesterone also play an important role in this process. In addition to the supply from circulation, several gonadal steroids are produced locally within the Purkinje cell (neurosteroids). In this chapter, the effect of thyroid and steroid hormones are separately discussed. Neurosteroids that are locally synthesized in the cerebellum are discussed in Chap. 42, “Neurosteroids and Synaptic Formation in the Cerebellum”.