Suppression of circulating calcitriol and duodenal active Ca transport by ketoconazole in pregnant rats.
Active Ca transport in the duodenum and the circulating level of calcitriol are elevated during pregnancy and lactation in the rat. Because calcitriol stimulates Ca transport in nonmated rats, we investigated its contribution to the increased transport during pregnancy and lactation. Rapid suppression of calcitriol from 28 +/- 3 to 8 +/- 0.4 pg/ml with the steroid hydroxylase inhibitor ketoconazole resulted in a 34% suppression of Ca transport in nonmated rats. At the end of pregnancy, when calcitriol concentration was suppressed from 64 +/- 7 to 12 +/- 2 pg/ml, the transport ratio decreased by 44%. Ca transport did not correlate with calcitriol levels between 40 and 80 pg/ml, suggesting a threshold level for maximal Ca transport stimulation. During lactation at even higher calcitriol levels, ketoconazole treatment again resulted in marked reduction in calcitriol from 124 +/- 1 to 71 +/- 12 pg/ml, but without any concurrent reduction in Ca transport in the duodenum. We conclude that in the vitamin D-replete rat the pregnancy-mediated, and probably also the lactation-mediated, increase in active Ca transport capacity is dependent on an increase in circulating calcitriol up to a certain threshold level.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002117:Calcitriol / Q000097:blood*; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D005260:Female; D007654:Ketoconazole / Q000494:pharmacology*; D007774:Lactation / Q000097:blood / Q000502:physiology; D009994:Osmolar Concentration; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002117:Calcitriol; D007654:Ketoconazole; D002118:Calcium