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 T(4), unchanged TSH) and also during thyrotoxicosis juvenile GPB5(-/-) mice had 25% lower serum T(4), compared to WT. During hypothyroidism, despite similar serum T(4), pituitary TSHbeta mRNA was 2-fold lower in GPB5(-/-) mice compared to WT. Adult mice displayed increased pituitary deiodinase type 2 during euthyroidism and decreased serum T(4) 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.