Sex steroid hormones are known to have gender-dependent effects on bone and cartilage in vivo and in vitro. To investigate whether this is a general property of steroids, or is specific to the sex steroid hormones, we examined whether the effects on bone of l,25-(OH)2D3 and 24,25(OH)2D3, the two active metabolites of vitamin D, are also gender-dependent. One-month-old male and female rats were treated for 1 month with various doses of 1,25-(OH)2D3, 24,25-(OH)2D3, or a combination of both metabolites. The direct effects of both metabolites on the skeleton of the treated animals were similar in male and female rats. 24,25-(OH)2D3 alone or in combination with l,25-(OH)2D3 increased bone calcium and phosphorus, while l,25-(OH)2D3 slightly decreased bone mineral content. 24,25-(OH)2D3 also enhanced the differentiation of cartilage in the growth plate, increasing the size of the hypertrophic zone. In addition, an increased metaphyseal bone volume was observed following 24,25-(OH)2D3 treatment in rats of both sexes, but not with l,25-(OH)2D3. Vitamin D metabolites affected the weight gain of the experimental animals in a gender-dependent manner; l,25-(OH)2D3 increased weight gain of male rats and 24,25-(OH)2D3 decreased weight gain of female rats. In addition, l,25-(OH)2D3 increased bone weight and ash weight in male animals. These gender-dependent effects of vitamin D metabolites may occur indirectly via effects of sex steroid hormones, the latter being a sex-related effect.
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