3 years ago

Thymic PTH Increases after Thyroparathyroidectomy in C57BL6/KaLwRij Mice.

Maurizio Zangari, Gareth J Morgan, Hanna Yoo, Larry J Suva, Bumjun Kim, Ikjae Shin, Donghoon Yoon, Ricky Edmonson
We previously reported a significant correlation between serum parathyroid hormone (PTH) levels and the myeloma response to proteasome inhibition suggesting crucial role for the PTH receptor 1 system in the control of myeloma tumor growth. While investigating the role of PTH in the anti-myeloma effect, the recovery of serum PTH levels after thyroparathyroidectomy (TPTX) was observed. Although the presence of thymus-derived PTH has been reported previously, the existence or role of thymic PTH in the serum remains controversial. Here, TPTX was performed in 8-12 week old C57BL6/KaLwRij mice to delineate the potential source(s) for the recovery of serum PTH. Immediately following TPTX, the expected loss of measurable serum PTH was observed. Serum PTH levels then recovered 3-4 weeks post-TPTX. In all, 13 endocrine organs from mice with recovered serum PTH were examined. The thymus from control mice expressed measurable and detectable Pth transcripts; however, the Pth transcript level was significantly elevated in tissue from TPTX mice. Western blot analysis of the thymus demonstrated a reproducible and distinct PTH band in thymus tissue that was significantly increased after TPTX. To directly confirm the identity of the distinct PTH band, immunoprecipitated proteins were isolated and subjected to tandem mass spectrometry. Following fragmentation and direct peptide sequencing, PTH peptides (1-13) and (54-70), diagnostic for PTH, were identified. These data demonstrate that the murine thymus produces PTH, and following TPTX, the thymus becomes the major source of serum PTH compensating for the loss of the parathyroid glands and returning circulating PTH levels to normal.

Publisher URL: http://doi.org/10.1210/en.2017-03083

DOI: 10.1210/en.2017-03083

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