Functional Evidence for the Presence of Type II 5’-Deiodinase in Somatotropes and Its Adaptive Role in Hypothyroidism

Abstract

The anterior pituitary contains abundant type II iodothyronine 5′-deiodinase (D2). The role of this enzyme in mediating thyroid hormone action in the pituitary has been proven only for thyrotropes, although there is evidence that it exists in other cell types, including somatotropes and lactotropes. Here we investigated the potential of D2 to mediate thyroid hormone regulation of growth hormone (GH). Using GH mRNA as an end point, we demonstrate that in hyperthyroid states GH mRNA levels are stimulated by triiodothyronine (T₃) generated via D1, whereas in hypothyroidism, when D2 activity is markedly increased, GH mRNA is more responsive to tetraiodothyronine (T₄) in a propylthiouracil-insensitive, reverse T₃-suppressible manner. Under short-term hyperthyroid conditions, GH levels correlate with plasma T₃; in contrast, the correlation is not observed in hypothyroidism, a condition in which plasma T₃ levels are too low to account for the response. These results add support to the concept that D2 is present in the pituitary and that the enzyme plays an important role in mediating stimulation of GH by thyroid hormones, particularly in hypothyroid states in which they could alleviate the impact of hypothyroxinemia on GH secretion.