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1,25-Dihydroxycholecalciferol Regulates Rat Intestinal Calbindin D_9k Posttranscriptionally^1,2,3,

Catherine Duflos^*, Claire Bellaton^*, Nathalie Baghdassarian^*, Mylène Gadoux^*, Danielle Pansu and Felix Bronner^,4

^* École Pratique des Hautes Études, INSERM U 45, Hôpital Edouard Herriot, 69437 Lyon, France Department of BioStructure and Function, The University of Connecticut Health Center, Farmington, CT 06030-3705

To determine whether calbindin D_9k (CaBP) is subject to posttranscriptional control, 6-wk-old Sprague Dawley-derived rats were fed one of three purified diets, 1.5% Ca and 3.0% Ca, mostly as carbonate, and 2.9% Ca, mostly as gluconate. Two weeks later, 5-cm segments of duodenum, jejunum, ileum, cecum and colon were obtained and analyzed for CaBP and CaBP-mRNA. Analysis of the steady-state distribution of CaBP-mRNA and of CaBP revealed a statistically significant (r = 0.95; P < 0.01) linear relationship between CaBP-mRNA and CaBP. When, however, animals that had been fed the 1.5% Ca diet received by intrajugular injection 1.2 nmol 1,25-dihydroxycholecalciferol [1,25-(OH)₂-D₃] and their CaBP-mRNA and CaBP were analyzed as a function of time after 1,25-(OH)₂-D₃ administration, the kinetic response of the two molecules differed. The CaBP-mRNA increased linearly by 68% for 4 h after administration and then declined over the next 6 h to a concentration below the preinjection value. Thus, appearance and disappearance of CaBP-mRNA approximated 17% · h^-1. The CaBP, however, increased steeply to 80% above preinjection concentration until 2 h postinjection, i.e., at a rate of 40% · h^-1. Thereafter, CaBP decreased to 35% above the preinjection value between 5 and 10 h postinjection (2.5% · h^-1). These findings are consistent with a 1,25-(OH)₂-D₃-mediated posttranscriptional regulation of CaBP concentrations, because the 1,25-(OH)₂-D₃-mediated increase in CaBP-mRNA is not reflected in an immediately changed CaBP level.

KEY WORDS: • transcriptional regulation • posttranscriptional regulation • calcium • vitamin D • rats

¹ Presented in part at the meeting of the American Society for Bone and Mineral Reserach, Baltimore, 9–13 September 1995. [Bronner, F., Bellaton, C., Duflos, C. & Pansu, D. (1995) Regulation of message and expression of intestinal rat calbindin D_9k (CaBP) by 1,25-(OH)₂-D₃].

² Support to C. Duflos by a joint grant from the Conseil Regional Rhône-Alpes and DIEPAL, Groupe DANONE, Villefrance-sur-Saône, France.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom reprint requests should be addressed.

Manuscript received 21 June 1995. Revision accepted 21 December 1995.