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Inverse relation between mRNA synthesis and secretion of parathyroid hormone in athymic mice grafted with human
A K Velin1, S Ander, K J Johansson
1Department of Biomedicine and Surgery, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
Abstract:
Parathyroid hormone (PTH) mRNA in original and transplanted human adenomatous parathyroid tissue and human serum intact PTH (S-iPTH) was measured in athymic mice at 4, 7, 14, and 28 days after transplantation. Parathyroid tissue was obtained during surgery for hyperparathyroidism and implanted subcutaneously. PTH mRNA detection was done with RT-PCR followed by membrane blot and hybridisation and S-iPTH was analysed using a human specific immunoradiometric method. At 4 days, PTH mRNA was 79.6+/-5.3% (mean+/-SE) of that in original tissue whereas S-iPTH was only 5.4 ng/l. At 28 days, PTH mRNA was significantly reduced to 60.7+/-4.1% whereas S-iPTH was increased to 192 ng/l. The reduced PTH mRNA expression in the transplants at 28 days may be explained by an inhibited DNA transcription. The presence of human S-iPTH in transplanted mice at 4 days may be due to cell disintegration and diffusion. The gradual increase in S-iPTH during the experimental period probably reflects increased transplant cell volume and improved graft revascularisation.
Insights
Transplanted human parathyroid tissue showed reduced parathyroid hormone (PTH) mRNA over time, while serum PTH levels gradually increased, suggesting improved graft function and revascularization in mice.
Area of Science:
- Endocrinology
- Molecular Biology
- Surgical Research
Background:
- Hyperparathyroidism necessitates surgical intervention, often involving parathyroid tissue removal.
- Understanding the behavior of transplanted parathyroid tissue is crucial for managing endocrine disorders.
Purpose of the Study:
- To investigate parathyroid hormone (PTH) mRNA expression and serum PTH levels in transplanted human adenomatous parathyroid tissue in vivo.
- To assess the functional recovery and viability of ectopic parathyroid grafts over time.
Main Methods:
- Human parathyroid adenoma tissue was subcutaneously transplanted into athymic mice.
- Parathyroid hormone (PTH) mRNA levels were quantified using RT-PCR and hybridization.
- Human serum intact PTH (S-iPTH) was measured using a human-specific immunoradiometric assay at multiple time points post-transplantation.
Main Results:
- At 4 days post-transplantation, PTH mRNA was approximately 80% of original levels, with minimal S-iPTH detected (5.4 ng/l).
- By 28 days, PTH mRNA significantly decreased to about 61% of original levels, while S-iPTH increased substantially to 192 ng/l.
- Early S-iPTH presence was attributed to cell disintegration, with later increases linked to augmented transplant cell volume and graft revascularization.
Conclusions:
- Reduced PTH mRNA expression in later stages may indicate inhibited DNA transcription in the transplanted tissue.
- The observed increase in serum PTH suggests successful graft function and vascularization over the experimental period.
- These findings provide insights into the physiological adaptation of ectopic parathyroid grafts.