Hyperparathyroidism and abnormal 1,25(OH)2 vitamin D3 metabolism in experimental lead intoxication.
Clinical evidence points to disturbed calcium metabolism in lead (Pb) intoxication. To further clarify the mechanisms involved, serum levels of 1,25(OH)2D3, receptors for 1,25(OH)2D3 as well as size and ultrastructure of parathyroid glands were examined in Wistar Kyoto rats exposed to 1% lead (Pb) acetate in drinking water for 10 weeks (short-term study) or 0.001-1% Pb acetate for 24 weeks (long-term study). After administration of Pb for 10 weeks, bone Pb was significantly increased (641 +/- 66.9 (SD) vs. 0.648 +/- 0.39 mg kg-1 ash in controls). Total serum calcium and ionized Ca2+ (1.15 +/- 0.031 vs. 1.25 +/- 0.03 mmol l-1) were significantly decreased. Renal function (Ccr) was unchanged, but urinary cAMP excretion and circulating 1,25(OH)2D3 (177 +/- 10.9 vs. 232 +/- 18.9 pmol l-1) were diminished. Specific binding of 1,25(OH)2D3 was increased in parathyroids (Bmax 128 +/- 4.7 vs. 108 +/- 0.6 fmol mg-1 protein) and intestinal muscosa; Bmax failed to adequately rise in response to pretreatment with 1,25(OH)2D3 (2 x 10 ng day-1 for 4 d) in Pb-exposed animals. Receptor characteristics (sedimentation constant, KD, DNA affinity) were unchanged. Parathyroid weight was significantly increased (178 +/- 25 vs. 96 +/- 34 micrograms) with no change of estimated nuclear volume, cell volume or cell ultrastructure. After 24 weeks of Pb exposure, a dose-dependent but non-linear increase of parathyroid weight was noted between 0.001% and 1% Pb in drinking fluid. The present study documents secondary hyperparathyroidism associated with, and presumably caused by, hypocalcaemia and low 1,25(OH)2D3 levels, in experimental Pb intoxication.
Szabo
A
A
Department of Internal Medicine, Ruperto Carola University, Heidelberg, Germany.
Merke
J
J
Hügel
U
U
Mall
G
G
Stoeppler
M
M
Ritz
E
E
D000818:Animals; D002117:Calcitriol / Q000097:blood*; D006962:Hyperparathyroidism, Secondary / Q000209:etiology* / Q000473:pathology; D006996:Hypocalcemia / Q000139:chemically induced / Q000150:complications; D007854:Lead / Q000633:toxicity*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D007854:Lead; D002117:Calcitriol