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Thymic PTH Increases After Thyroparathyroidectomy in C57BL/KaLwRij Mice.

Abstract

We previously reported a substantial correlation between serum parathyroid hormone (PTH) levels and the myeloma response to proteasome inhibition that suggests a crucial role for the PTH receptor 1 system in the control of myeloma tumor growth. While investigating the role of PTH in the antimyeloma effect, we observed the recovery of serum PTH levels after thyroparathyroidectomy (TPTX). 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- to 12-week-old C57BL/KaLwRij mice to delineate the potential source(s) for the recovery of serum PTH. Immediately after TPTX, the expected loss of measurable serum PTH was observed. Serum PTH levels recovered 3 to 4 weeks after TPTX. Thirteen 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 substantially 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. After fragmentation and direct peptide sequencing, PTH peptides PTH(1-13) and PTH(54-70), diagnostic for PTH, were identified. These data demonstrate that the murine thymus produces PTH and that after 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.

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  • Authors+Show Affiliations

    ,

    Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

    ,

    Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

    ,

    Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

    ,

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.

    ,

    Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

    ,

    Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

    ,

    Department of Veterinary Physiology & Pharmacology, Texas A&M University, College Station, Texas.

    Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

    Source

    Endocrinology 159:4 2018 04 01 pg 1561-1569

    MeSH

    Animals
    Calcium
    Mice
    Mice, Inbred C57BL
    Parathyroid Hormone
    Parathyroidectomy
    Thymus Gland
    Thyroidectomy

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    29381784

    Citation

    Zangari, Maurizio, et al. "Thymic PTH Increases After Thyroparathyroidectomy in C57BL/KaLwRij Mice." Endocrinology, vol. 159, no. 4, 2018, pp. 1561-1569.
    Zangari M, Yoo H, Shin I, et al. Thymic PTH Increases After Thyroparathyroidectomy in C57BL/KaLwRij Mice. Endocrinology. 2018;159(4):1561-1569.
    Zangari, M., Yoo, H., Shin, I., Kim, B., Edmondson, R., Morgan, G. J., ... Yoon, D. (2018). Thymic PTH Increases After Thyroparathyroidectomy in C57BL/KaLwRij Mice. Endocrinology, 159(4), pp. 1561-1569. doi:10.1210/en.2017-03083.
    Zangari M, et al. Thymic PTH Increases After Thyroparathyroidectomy in C57BL/KaLwRij Mice. Endocrinology. 2018 04 1;159(4):1561-1569. PubMed PMID: 29381784.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Thymic PTH Increases After Thyroparathyroidectomy in C57BL/KaLwRij Mice. AU - Zangari,Maurizio, AU - Yoo,Hanna, AU - Shin,Ikjae, AU - Kim,Bumjun, AU - Edmondson,Ricky, AU - Morgan,Gareth J, AU - Suva,Larry J, AU - Yoon,Donghoon, PY - 2017/11/02/received PY - 2018/01/08/accepted PY - 2018/1/31/pubmed PY - 2018/11/28/medline PY - 2018/1/31/entrez SP - 1561 EP - 1569 JF - Endocrinology JO - Endocrinology VL - 159 IS - 4 N2 - We previously reported a substantial correlation between serum parathyroid hormone (PTH) levels and the myeloma response to proteasome inhibition that suggests a crucial role for the PTH receptor 1 system in the control of myeloma tumor growth. While investigating the role of PTH in the antimyeloma effect, we observed the recovery of serum PTH levels after thyroparathyroidectomy (TPTX). 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- to 12-week-old C57BL/KaLwRij mice to delineate the potential source(s) for the recovery of serum PTH. Immediately after TPTX, the expected loss of measurable serum PTH was observed. Serum PTH levels recovered 3 to 4 weeks after TPTX. Thirteen 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 substantially 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. After fragmentation and direct peptide sequencing, PTH peptides PTH(1-13) and PTH(54-70), diagnostic for PTH, were identified. These data demonstrate that the murine thymus produces PTH and that after 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. SN - 1945-7170 UR - https://www.unboundmedicine.com/medline/citation/29381784/Thymic_PTH_Increases_After_Thyroparathyroidectomy_in_C57BL/KaLwRij_Mice L2 - https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2017-03083 DB - PRIME DP - Unbound Medicine ER -