Suppression of circulating calcitriol and duodenal active calcium
transport by ketoconazole in pregnant rats.
Boass, Agna, and Svein U. Toverud.
Department of Pharmacology, School of Medicine, and Dental Research
Center, School of Dentistry, University of North Carolina at Chapel
Hill, NC 27599
APStracts 2:0133E, 1995.
Active calcium transport in the duodenum and circulating level of
calcitriol are elevated during pregnancy and lactation in the rat.
Because calcitriol stimulates calcium 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.
Received 28 Februrary 1995; accepted in final form 8 June 1995.
APS Manuscript Number E95-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.