title: Regulation of parathyroid cell gene expression in experimental uremia.
abstract: The secondary hyperparathyroidism of renal failure is an important component of renal osteodystrophy. We studied PTHmRNA levels and their regulation in control and subtotal nephrectomized (5/6 NX) rats at 3 wk, as well as levels of the 1,25(OH)2D3 receptor mRNA in parathyroids. Serum 1,25(OH)2D levels were decreased in 5/6 NX, whereas PTHmRNA levels were increased (7 +/- 0.7 OD U, N = 4) compared to controls (2.1 +/- 1.2, P less than 0.01); both decreased after 1,25(OH)2D3 (100 pmol/100 g body weight). Similar results were found in 5/6 NX rats after 3 months. There was no change in actin mRNA levels. PTHmRNA levels were highest in 5/6 NX rats with the most severe renal failure. The parathyroid gland 1,25(OH)2D3 receptor mRNA levels were not different between 5/6 NX rats and controls and were not affected by 1,25(OH)2D3 (100 pmol/100 g body weight daily) at 1 or 3 days. PTHmRNA levels of 5/6 NX rats did not increase when the serum calcium was decreased from 2.8 +/- 0.05 mmol/L to 0.9 +/- 0.15 mmol/L at 3 or 5 h, which contrasted with the marked increase in PTHmRNA in normal rats after hypocalcemia. As in normal rats, after hypercalcemia (4.8 mmol/L at 1 h) there was no change in the 5/6 NX rats' PTHmRNA levels. These results show that 5/6 NX rats have increased PTHmRNA levels that are normally regulated by injected 1,25(OH)2D3 but not by calcium. Parathyroid gland 1,25(OH)2D receptor mRNA levels are not increased in 5/6 NX in contrast to the increased PTHmRNA, which reflects the larger glands of uremia. 1,25(OH)2D receptor mRNA levels were not regulated by 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Nephrology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Shvil
authors.forename: T
authors.initials: T
authors.lastname: Naveh-Many
authors.forename: P
authors.initials: P
authors.lastname: Barach
authors.forename: J
authors.initials: J
authors.lastname: Silver
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000097:blood / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008297:Male; D009392:Nephrectomy; D010280:Parathyroid Glands / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014511:Uremia / Q000150:complications / Q000235:genetics* / Q000378:metabolism
chemical_list: D010281:Parathyroid Hormone; D012333:RNA, Messenger; D002117:Calcitriol; D002118:Calcium