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American Journal of Pathology, Vol 150, 861-871, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

Co-secretion of parathyroid hormone and parathyroid-hormone-related protein via a regulated pathway in human parathyroid adenoma cells

H Matsushita, M Usui, M Hara, Y Shishiba, H Nakazawa, K Honda, K Torigoe, K Kohno and M Kurimoto
Department of Pathology, Toranomon Hospital, Tokyo, Japan.

Parathyroid-hormone-related protein (PTHrP) is widely expressed not only in malignant tumors but also in both epithelial and nonepithelial cells of normal tissues. Secreted PTHrP is suspected to act as a paracrine or autocrine regulator. However, little is known about its secretory pathway. To cast light on this question, we studied the intracytoplasmic distribution of parathyroid hormone (PTH) and PTHrP immunohistochemically and immunoelectron microscopically in 10 surgically resected parathyroid adenomas. Double immunostaining was performed using anti-PTH antibody and a newly established anti-PTHrP antibody to reveal the relationship between their two distributions. Additional examination by cell immunoblot assay was performed to determine whether both PTH and PTHrP are secreted simultaneously. Both PTH and PTHrP were actually secreted from individual parathyroid cells simultaneously on cell immunoblot assay. Immunohistochemically, there were two different types of adenoma cells, i.e., one positive only for PTH and the other positive for both PTH and PTHrP. PTH was distributed linearly or fine granularly along the cytoplasmic membrane, whereas PTHrP was distributed diffusely or coarse granularly in the cytoplasm. The intracytoplasmic distributions of PTH and PTHrP often overlapped. Immunoelectron microscopical examination demonstrated that PTHrP co- localized with PTH in the same secretory granules. The results clearly demonstrated that PTHrP can be co-secreted with PTH via a regulated pathway using secretory granules.




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Copyright © 1997 by the American Society for Investigative Pathology.