Thyroid hormone-responsive pituitary hyperplasia independent of somatostatin receptor 2

Mice homozygous for the targeted disruption of the glycoprotein hormone alpha -subunit (alpha Gsu) display hypertrophy and hyperplasia of the anterior pituitary thyrotropes. Thyrotrope hyperplasia results in tumors in aged alpha Gsu(-/-) mice. These adenomatous pituitaries can grow independently as intrascapular transplants in hypothyroid mice, suggesting that they have progressed beyond simple hyperplasia. We used magnetic resonance imaging to follow the growth and regression of thyrotrope adenomatous hyperplasia in response to thyroid hormone treatment and discovered that the tumors retain thyroid hormone responsiveness. Somatostatin (SMST) and its diverse receptors have been implicated in cell proliferation and tumorigenesis. To test the involvement of SMST receptor 2 (SMSTR2) in pituitary tumor progression and thyroid hormone responsiveness in alpha Gsu(-/-) mutants, we generated Smstr2(-/-), alpha Gsu(-/-) mice. Smstr2(-/-), alpha Gsu(-/-) mice develop hyperplasia of thyrotropes, similar to alpha Gsu-/- mutants, demonstrating that SMSTR2 is dispensable for the development of pituitary adenomatous hyperplasia. Thyrotrope hyperplasia in Smstr2(-/-), alpha Gsu(-/-) mice regresses in response to T-4 treatment, suggesting that SMSTR2 is not required in the T-4 feedback loop regulating TSH secretion.