Apoptosis in parathyroid hyperplasia of patients with primary or secondary uremic hyperparathyroidism.
BACKGROUND
Chronic oversecretion of parathyroid hormone (PTH) is associated with parathyroid hyperplasia, reflecting a disturbed balance between cell proliferation and apoptosis. This study addressed the unsolved issue of apoptosis in hyperparathyroidism.


METHODS
Parathyroid glands from 19 patients with primary (1 degrees ) and 11 patients with secondary (2 degrees ) uremic hyperparathyroidism, as well as 13 normal parathyroid glands, were examined. Apoptosis was evaluated by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick end-labeling assay (TUNEL). Because the apoptotic process is regulated by several oncoproteins, the expression of Bcl-2 and Bax was analyzed by immunohistochemistry.


RESULTS
The numbers of apoptotic cells in 1 degrees parathyroid adenoma (0.99 +/- 0.03 per 1000 cells, mean +/- SE, P < 0.009) and 2 degrees parathyroid hyperplasia (1.20 +/- 0.54 per 1000 cells, P < 0.005) were significantly higher than in normal parathyroid tissue (0.13 +/- 0. 06 per 1000 cells). Light microscopy examination of hyperplastic parathyroid tissue from a uremic patient showed the presence of nuclei with dense chromatin characteristic of apoptosis. Bcl-2 staining was strong in normal tissues but weak or negative in several sections of 1 degrees and 2 degrees hyperparathyroid tissues, mostly in nodular areas. Bax staining was homogeneous in normal tissue but patchy in several hyperplastic tissues.


CONCLUSIONS
These results suggest that hyperparathyroidism is associated with a compensatory increase in apoptosis, possibly favored by a diminished Bcl-2/Bax ratio. This renders highly improbable the hypothesis that parathyroid hyperplasia is due to a decreased rate of apoptosis.
Zhang
P
P
Unité 507 de l'INSERM, Division of Nephrology, and Unité 345 de l'INSERM, Hôpital Necker, Paris, France.
Duchambon
P
P
Gogusev
J
J
Nabarra
B
B
Sarfati
E
E
Bourdeau
A
A
Drüeke
T B
TB
D017209:Apoptosis; D053938:DNA Fragmentation; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000473:pathology*; D006965:Hyperplasia; D020287:In Situ Nick-End Labeling; D010280:Parathyroid Glands / Q000737:chemistry / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014511:Uremia / Q000473:pathology*; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000032:analysis
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor