A Glycoprotein Hormone Expressed in Corticotrophs Exhibits Unique Binding Properties on Thyroid-Stimulating Hormone Receptor

Corticotroph-derived glycoprotein hormone (CGH), also referred to as thyrostimulin, is a noncovalent heterodimer of glycoprotein hormone α 2 (GPHA2) and glycoprotein hormone β 5 (GPHB5). Here, we demonstrate that both subunits of CGH are expressed in the corticotroph cells of the human anterior pituitary, as well as in skin, retina, and testis. CGH activates the TSH receptor (TSHR); 125I-CGH binding to cells expressing TSHR is saturable, specific, and of high affinity. In competition studies, unlabeled CGH is a potent competitor for 125I-TSH binding, whereas unlabeled TSH does not compete for 125I-CGH binding. Binding and competition analyses are consistent with the presence of two binding sites on the TSHR transfected baby hamster kidney cells, one that can interact with either TSH or CGH, and another that binds CGH alone. Transgenic overexpression of GPHB5 in mice produces elevations in serum T4 levels, reductions in body weight, and proptosis. However, neither transgenic overexpression of GPHA2 nor del...