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1,25-Dihydroxycholecalciferol Analogs Cannot Replace Vitamin D in Normocalcemic Male Rats^{1, 2, 3,}

Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706

A possible role of vitamin D in the growth and development of rats was investigated. Impaired development was observed in normocalcemic, vitamin D-deficient male and female rats, as revealed by low intestinal calcium transport, low renal vitamin D receptor levels and poor bone mineralization. Analogs of 1,25-dihydroxycholecalciferol, possessing reduced calcium-mobilizing activity in intestine and bone but retaining differentiation activity in cultured cells, were unable to support normal development of normocalcemic, vitamin D-deficient male rats. These results suggest that either the calcium-mobilizing activity alone or both the calcium-mobilizing activity and differentiating activity of vitamin D are required for normal development or that the analogs are inactive in vivo. We also demonstrated sex-related differences in intestinal calcium transport, renal vitamin D receptor regulation and bone mineralization that were independent of vitamin D status.

KEY WORDS: • vitamin D • development • rats • 1,25-dihydroxycholecalciferol analogs • calcium

¹ Supported in part by program project grant no. DK14881 from the National Institutes of Health and by funds from the Wisconsin Alumni Research Foundation.

² 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.

³ No reprints will be available from the authors.

⁴ To whom correspondence should be addressed.

Manuscript received 23 February 1993. Revision accepted 24 June 1993.