Modulation by vitamin D status of the responsiveness of rat bone to gonadal steroids.
We have previously demonstrated that gonadal steroids stimulate [3H]thymidine incorporation and creatine kinase specific activity in skeletal tissues. In the present study we report that in 20-day-old vitamin D-deficient Wistar-derived rats, 17 beta-estradiol (E2; 5 micrograms/rat) or testosterone (50 micrograms/rat) failed to stimulate [3H]thymidine incorporation into diaphyses of long bones and that the response to these hormones in terms of increased creatine kinase specific activity was less than half the value in normally fed rats. Two daily ip injections of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3; 0.5 ng/g BW], but not 24,25-(OH)2D3 (5 ng/g BW), partially restored the biological responses to E2 in bone of 21-day-old vitamin D-deficient female rats. Vitamin D deficiency did not impair the responsiveness to gonadal steroids in the epiphysis of long bones, uterus, or prostate, in contrast to its effect on diaphysis. In 21-day-old normally fed female rats, neither vitamin D metabolite enhanced the response to E2. When cultures of rat epiphyseal cells were treated daily for 5 days with either 1,25-(OH)2D3 (1 nM) or 24,25-(OH)2D3 (10 nM), followed by E2 (30 nM) for 24 h, creatine kinase activity was significantly higher than in cultures treated daily for 5 days with vehicle alone, and then with E2. The same treatment of rat embryo calvaria bone cells showed that 1,25-(OH)2D3, but not 24,25-(OH)2D3, significantly increased the creatine kinase activity response to E2. These findings suggest that vitamin D metabolites selectively affect the biological responses of skeletal tissues to gonadal steroids.
Sömjen
D
D
Hard Tissues Unit, Ichilov Hospital, Sackler School of Medicine, Tel Aviv University, Israel.
Kaye
A M
AM
Harell
A
A
Weisman
Y
Y
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D002117:Calcitriol / Q000494:pharmacology; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D004351:Drug Resistance; D004958:Estradiol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012886:Skull / Q000166:cytology / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*; D014807:Vitamin D / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000503:physiopathology
D014807:Vitamin D; D013739:Testosterone; D004958:Estradiol; D002117:Calcitriol