1,25 dihydroxycholecalciferol-mediated calcium absorption and gene expression are higher in female than in male mice.
Recent advances in bone and calcium (Ca) metabolism have relied upon genetically modified mice. However, although human studies have identified gender as an important modulator of Ca metabolism, its effect on Ca metabolism has not been examined in mice. Here we examined basal and vitamin D-regulated Ca absorption (in situ ligated loops) and mRNA levels for the apical membrane calcium channel, TRPV6, and the calcium binding protein, calbindin D(9k) (CaBP) mRNA levels (real-time PCR) in duodenum of female and male mice. At 2 mo of age, females fed a 5 g Ca/kg diet had higher Ca absorption (62.3 +/- 4.8 vs. 47 +/- 3.6%) and TRPV6 mRNA levels than males even though plasma 1,25 dihydroxyvitamin D [1,25(OH)(2) D] was not different. In mice fed high (20 g/kg), normal (5 g/kg), or low (0.2 g/kg) Ca diets for 7 d to alter plasma 1,25(OH)(2) D (91 +/- 12, 322 +/- 25, and 587 +/- 43 pmol/L, respectively), the relation between Ca absorption (slope = 0.116 vs. 0.084, P = 0.021) or duodenum TRPV6 mRNA (slope = 0.042 vs. 0.025, P = 0.034) and circulating 1,25(OH)(2) D was steeper in females. After a single 1,25(OH)(2) D injection (200 ng/100 g body weight), peak induction of TRPV6 mRNA was 2-fold greater (at 6 h) and CaBP mRNA was 20% higher in females (at 16 h). Duodenal vitamin D receptor mRNA levels did not differ between genders. Our data indicate that female mice are more sensitive to changes in serum 1,25(OH)(2) D levels than males and that this must be considered when using mice to study calcium and bone biology.
Department of Foods and Nutrition and the Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907, USA.
Yurong
Y
Song
James C
JC
Fleet
D000818:Animals; D064026:Calbindins; D002117:Calcitriol / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002136:Calcium, Dietary / Q000378:metabolism* / Q000493:pharmacokinetics; D004032:Diet; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D012313:RNA / Q000302:isolation & purification; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D012727:Sex Characteristics; D050916:TRPV Cation Channels
D064026:Calbindins; D015220:Calcium Channels; D002136:Calcium, Dietary; D064030:S100 Calcium Binding Protein G; D050916:TRPV Cation Channels; C120776:TRPV6 channel; D012313:RNA; D002117:Calcitriol