Abstract

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 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 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.

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