CTH and hypothyroidism: Thus, hyperthyroidism is associated with negative regulation of CGL expression through direct binding and repression of the CGL locus by T3-bound TRβ1, while hypothyroidism is associated with increased CGL expression indirectly through derepression of the transcriptional activator ATF4, possibly by hypothyroidism-induced endoplasmic reticulum stress (Zhou et al., 2016).