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Stimulating parathyroid cell proliferation and PTH release with phosphate in organ cultures obtained from patients with primary and secondary hyperparathyroidism for a prolonged period

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Abstract

The pathogenesis of primary hyperparathyroidism (I°-HPT) and secondary hyperparathyroidism (II°-HPT) remains to be elucidated. To characterize their pathophysiology, we investigated the effects of calcium and phosphate on cell proliferation and PTH release in an organ culture of parathyroid tissues. Dissected parathyroid tissues obtained from patients with I°-HPT (adenoma) or II°-HPT (nodular hyperplasia) were precultured on a collagen-coated membrane for 1–4 week. After changing the medium for one containing various concentrations of phosphate, PTH release and [3H]thymidine incorporation were studied. In contrast to dispersed parathyroid cells cultured in a monolayer, calcium decreased PTH release in a concentration-dependent manner in parathyroid tissues. Furthermore, when parathyroid tissues obtained from II°-HPT were precultured for 1–4 weeks, PTH release and parathyroid cell proliferation were significantly increased in high-phosphate medium. These phosphate effects were also observed to a lesser extent in parathyroid tissues obtained from I°-HPT, but there was no significant difference between I°-HPT and II°-HPT. Microarray analyses revealed that mRNA levels of PTH, CaSR, and VDR were well preserved, and several growth factors (e.g. TGF-beta1-induced protein) were abundantly expressed in II°-HPT. Using organ cultures of hyperparathyroid tissues, in which PTH release and CaSR are well preserved for a prolonged period, we have demonstrated that phosphate stimulates parathyroid cell proliferation not only in II°-HPT but also in I°-HPT. Although the mechanism responsible for phosphate-induced cell proliferation remains to be elucidated, our in vitro findings suggest that both parathyroid tissues preserve to some extent a physiological response system to hyperphosphatemia as observed in normal parathyroid cells.

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Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (no. 15390296, 17590967 and 20591102).

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Authors and Affiliations

  1. Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women’s Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo, 162-8666, Japan

    Kishiko Nakajima, Kazue Takano & Kanji Sato

  2. Teijin Pharmaceutical Co, Asahigaoka 4-3-2, Hino, Tokyo, 191-8512, Japan

    Ken-ichi Umino & Yoshiaki Azuma

  3. Central Research Institute, Tokyo Women’s Medical University, Tokyo, Japan

    Seiichi Kosaka

  4. Department of Surgery, Institute of Clinical Endocrinology, Tokyo Women’s Medical University, Tokyo, Japan

    Takao Obara

  5. Field of Pathophysiology and Treatment of Thyroid and Parathyroid Disease, Division of Internal Medicine, Graduate School of Medicine, Tokyo Women’s Medical University, Tokyo, Japan

    Kanji Sato

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  1. Kishiko Nakajima
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Correspondence to Kanji Sato.

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Nakajima, K., Umino, Ki., Azuma, Y. et al. Stimulating parathyroid cell proliferation and PTH release with phosphate in organ cultures obtained from patients with primary and secondary hyperparathyroidism for a prolonged period. J Bone Miner Metab 27, 224–233 (2009). https://doi.org/10.1007/s00774-008-0032-8

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  • DOI: https://doi.org/10.1007/s00774-008-0032-8

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