TSHB and hypothyroidism: However, when animals who possessed no TRs (TRα1−/−β−/−) were rendered to hypothyroidism, their serum TSH and TSHβ mRNA levels in the pituitary were equivalent to those in the wild-type mice, demonstrating that TRs are not required and not involved with the up-regulation of the TSH gene in the hypothyroid status [59].