A new analog of calcitriol, 19-nor-1,25-(OH)2D2, suppresses parathyroid hormone secretion in uremic rats in the absence of hypercalcemia.
The active metabolite of vitamin D, calcitriol (1 alpha,25-(OH)2D3), suppresses parathyroid hormone (PTH) gene transcription. Although 1 alpha,25-(OH)2D3 is effective in suppressing secondary hyperparathyroidism (SH) in uremic patients, the mandatory use of large amounts of calcium salts to control serum phosphorus may preclude, in some patients, the use of ideal therapeutic doses of 1 alpha,25-(OH)2D3 because of hypercalcemia. We have studied a new analog of calcitriol, 19-nor-1 alpha,25-(OH)2D2, that possesses low calcemic and phosphatemic activity. Uremic rats received vehicle, 1 alpha,25-(OH)2D3 (2.0, 4.0, or 8.0 ng/rat) or 19-nor-1,25-(OH)2D2 (8.0, 25 or 75 ng/rat) intraperitoneally (IP) every other day for a period of 8 days. Pretreatment and posttreatment values of intact PTH were measured. The normal values for rat intact-PTH were 22 +/- 4.2 pg/mL and for ionized calcium (ICa) 4.77 +/- .07 mg/dL. The only dose of 1 alpha,25-(OH)2D3 that achieved a significantly, suppressed PTH (P < 0.01) was the 8.0 ng/rat. PTH decreased from 202 +/- 31 to 90 +/- 20 pg/mL. However, ICa increased from 4.81 +/- 0.08 to 5.08 mg/dL from uremic control (P < 0.02). Conversely, all doses of 19-nor-1,25-(OH)2D2 were effective in suppressing PTH, and none produced an elevation in ICa that was significantly different from that of vehicle-treated uremic rats. The maximum effect was achieved with the 75 ng/rat dose, which decreased PTH from 193 +/- 49 to 53 +/- 16 pg/mL (a decrease in 72.5%).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002417:Cattle; D002478:Cells, Cultured; D003401:Creatine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006934:Hypercalcemia / Q000150:complications; D010280:Parathyroid Glands / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000097:blood / Q000150:complications / Q000503:physiopathology*
D010281:Parathyroid Hormone; D010758:Phosphorus; D002117:Calcitriol; D003401:Creatine; D002118:Calcium