Comparative analysis and functional implications of ligand dependent changes in estrogen- and
thyroid hormone receptor expression in the developing cerebellum
Abstract
Trophic hormones are important regulators of CNS development and function. In particular,
estrogen (E2) and thyroid hormones (THs) regulate cell migration, differentiation,
proliferation and synaptogenesis/network formation during cerebellar development. These
hormone-regulated events involve the binding of hormone ligands to their cognate receptors
that function as transcription factors to activate relevant genes for the adequate orchestration
of developmental processes. Recent reports implicate a complex mechanism through which
E2 and THs influence the expression levels of each other’s receptors (ERs and TRs) to
precisely mediate developmental signals. Here we examined the effects of the presence or
absence of E2 and THs on the expression levels of their receptor mRNAs and proteins.
Cerebellar granule cell cultures were treated with either E2, T3, T4 or a combination of these
hormones, and resulting receptor expression levels were determined by quantitative PCR and
Western blot techniques. Results were compared to non-treated controls and to samples
obtained from 14-day-old in situ cerebella. Additionally, we determined the effects that glial
cells might have on the regulation of ER-TR expression levels. Results show that: (i) ER and
TR expression levels depend on the individual or combined presence/absence of E2 and THs;
(ii) glial cells are important mediators in the hormonal regulation of neuronal ER-TR
expression, and (iii) loss of tissue integrity results in characteristic changes in ER-TR
expression levels. These observations suggest that both E2 and THs are required for the
precise orchestration of cerebellar development and that alterations in the tissue concentration
of either of the hormones may influence signaling mechanisms that are driven by both E2 and
THs. Comparison of data from in vitro and in situ samples also revealed a shift in receptor
expression levels after loss of tissue integrity, likely indicating possible adjusting/regenerative
mechanisms after cerebellar tissue injury
