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".

Exploring the role of testosterone in the cerebellum link to neuroticism: From adolescence to early adulthood

“…Specifically, the binding of oestradiol to androgen receptors has been thought to produce both functional and organizational effects on the cerebellum (Haraguchi et al, 2012;Napolitano et al, 2014). The discovery that oestradiol has protective effects on the cerebellum (Hedges et al, 2012;Sasahara et al, 2007) raises the possibility that hormonal effects on neuroticism and cerebellar gray matter in women are mediated through oestradiol (Koibuchi and Ikeda 2013). Synthesis of oestradiol and testosterone depends on progesterone which has shown to promote dendritic growth, spinogenesis, and synaptogenesis of Purkinje cells (Dean et al, 2008;Tsutsui, 2013).…”

Sex Differences in Resting-State Functional Connectivity of the Cerebellum in Autism Spectrum Disorder

“…Another motivating factor for investigating the cerebellum in the context of sex differences in ASD is the simultaneous co-expression of ASD candidate genes and rising gonadal steroids that promote neural growth (Koibuchi and Ikeda, 2013) in this same region during development (Menache et al, 2013; Willsey et al, 2013; Wang et al, 2014). Studies conducted using selectively bred mice have suggested that sex steroids mediate cerebellar neurodegeneration, and also that estrogens may have a protective effect on localized neural development (Dean and McCarthy, 2008; Biamonte et al, 2009).…”

Thyroid Hormone Role on Cerebellar Development and Maintenance: A Perspective Based on Transgenic Mouse Models

“…The cerebellum was one of the first targets of THs to be identified, and it is a useful model for studying the mechanisms by which THs influence the CNS. In particular, the cerebellum has a relatively homogenous and simple structure with a well-characterized laminar organization and a small number of cell types that develop within spatially defined regions (9–11). …”