Background: The purpose of this study was to clarify the relationships of extractable and secreted parathyroid hormone (PTH) and parathyroid secretory protein (PSP) in human parathyroid tumors to PTH messenger RNA (mRNA), PSP mRNA, and cell replication.
Methods and results: In tissue cultures of seven adenomas and five secondary hyperplasias, we found a direct correlation for secreted PTH versus PSP for both adenomas and secondary hyperplasias. Secreted PTH:PSP was elevated for adenomas (11:1) compared to that of secondary hyperplasias (2:1), and adenomas secreted significantly more PTH and PSP than did secondary hyperplasias. In extracts of eight adenomas and six secondary hyperplasias, the ratio of PTH:PSP was unexpectedly low (2:1) and similar for both adenomas and secondary hyperplasias. The ratio of extractable PTH mRNA:PSP mRNA was extremely low for both adenomas (1:7) and for secondary hyperplasias (1:5). Flow cytometry indicated that percent replication was inversely correlated with PTH mRNA and PSP mRNA.
Conclusions: Increased PTH secretion by adenomas cannot be attributed to increased biosynthetic capacity because it is less than expected. Hypersecretion of PTH by adenomas and coincident marked reductions in PTH mRNA suggest either a defect in cytoplasmic storage of PTH or impairment of normal posttranslational degradation of PTH. As parathyroid tumor cells increase replication, PTH mRNA is reduced. Possible explanations for this include decreased PTH gene transcription or decreased mRNA half-life.