Expression of GCMB by Intrathymic Parathyroid Hormone-Secreting Adenomas Indicates Their Parathyroid Cell Origin

Abstract

GCMA and GCMB are related transcription factors that are critically important for embryological development of the placenta and parathyroid glands, respectively. Mice in which parathyroid glands have been surgically removed or fail to develop due to genetic loss of GCMB show continued production of PTH from a subset of thymic cells that express GCMA. In this study we examined whether human thymus produces PTH and/or GCMA and whether intrathymic PTH-secreting adenomas express GCMA or GCMB to determine the embryological origin of the secretory cells. By contrast to mouse thymus, analysis of 22 samples of human thymus tissue by RT-PCR and/or immunohistochemistry failed to demonstrate the expression of either PTH or GCMA. RT-PCR analysis of 16 intrathymic adenomas from patients with surgically cured primary hyperparathyroidism showed that these tumors expressed PTH and GCMB and not GCMA. We conclude that the normal human thymus does not express GCMA or PTH, and therefore, in contrast to the mouse, the human thymus is not a source of PTH production. Finally, intrathymic PTH-secreting adenomas express the parathyroid-specific GCMB gene, which suggests that these tumors were derived from parathyroid cells that migrated errantly during embryogenesis.