AJP - Endocrinology and Metabolism, Vol 269, Issue 5 E934-E939, Copyright © 1995 by American Physiological Society
Suppression of circulating calcitriol and duodenal active Ca transport by ketoconazole in pregnant rats
A. Boass and S. U. Toverud
Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill 27599, USA.
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.
