Hyperplasia of the parathyroid gland without secondary hyperparathyroidism.
BACKGROUND
Low dietary phosphorus (P) prevents parathyroid gland (PTG) hyperplasia and the development of secondary hyperparathyroidism (SH) in uremic rats. The present study explores the effects of P restriction on parathyroid hormone (PTH) synthesis and secretion and PT cell growth in rats with established SH and PTG hyperplasia.


METHODS
Normal and 5/6 nephrectomized rats were fed a high P (0.8%) diet. After two weeks, the normal rats and half of the uremic rats were sacrificed (U-HP) while the remaining uremic rats were switched to a low P (0.2%) diet (U-HP-LP).


RESULTS
High dietary P induced a significant increase in serum P, PTH, and PTG weight, but not ionized calcium compared to normal animals fed the same diet (N-HP). P restriction returned serum P and PTH to normal levels by one week. In contrast, PTG size did not regress and glands remained enlarged for up to eight weeks with no evidence of apoptosis. Ribonuclease protection assay and metabolic labeling studies demonstrated similar PTH/actin mRNA ratios and 35S-labeled PTH among the three groups. Intracellular intact PTH was higher in U-HP and U-HP-LP rats compared to N-HP animals with no differences between the two uremic groups. PTG-PTH content correlated only with PTG weight, and serum PTH only with serum P. The PTG secretory response to calcium remained intact.


CONCLUSIONS
In established chief-cell hyperplasia, P restriction restores normal serum PTH levels without affecting PTG hyperplasia, PTH synthesis, PTG cytosolic PTH or the PTH secretory response to calcium, suggesting an impaired exocytosis of PTH.
Takahashi
Fumiaki
F
Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Denda
Masashi
M
Finch
Jane L
JL
Brown
Alex J
AJ
Slatopolsky
Eduardo
E
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006961:Hyperparathyroidism / Q000178:diet therapy* / Q000473:pathology*; D006965:Hyperplasia; D007425:Intracellular Membranes / Q000378:metabolism; D010280:Parathyroid Glands / Q000378:metabolism / Q000473:pathology*; D010281:Parathyroid Hormone / Q000378:metabolism; D016226:Phosphorus, Dietary / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010281:Parathyroid Hormone; D016226:Phosphorus, Dietary