Transient hypothyroxinemia in juvenile glycoprotein hormone subunit B5 knock-out mice

The heterodimer thyrostimulin, comprised of two novel glycoprotein hormone subunits GPA2 and GPB5, activates the TSH receptor. To understand its role in the regulation of the hypothalamus–pituitary–thyroid (HPT-) axis, we evaluated juvenile and adult GPB5 knock-out (GPB5−/−) and wild type mice (WT) during euthyroidism, hypothyroidism and thyrotoxicosis. Surprisingly, juvenile euthyroid GPB5−/− mice displayed marked hypothyroxinemia (25% lower serum T4, unchanged TSH) and also during thyrotoxicosis juvenile GPB5−/− mice had 25% lower serum T4, compared to WT. During hypothyroidism, despite similar serum T4, pituitary TSHβ mRNA was 2-fold lower in GPB5−/− mice compared to WT. Adult mice displayed increased pituitary deiodinase type 2 during euthyroidism and decreased serum T4 during hypothyroidism in GPB5−/−. Thus, lacking GPB5 results in moderate deviations of the HPT-axis. The more pronounced differences observed in juvenile mice compared to adult mice are in agreement with the notion that GPB5 has a role during development.