Interaction of androgen and 1,25-dihydroxyvitamin D3: effects on normal rat bone cells

We studied the actions of testosterone (T) and 5 alpha-dihydrotestosterone (DHT) in combination with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on primary rat bone cells. The actions of androgens were generally anabolic, although response patterns varied considerably between cultures. For example, DHT caused striking dose- and time-dependent increases in [3H]thymidine incorporation into calvarial cells over the range 1-100 nM, with maximal stimulation of 2.5-fold after 9 days in culture. Testosterone (50 nM) also stimulated [3H]thymidine incorporation into long bone-derived cells. 1,25-(OH)2D3 generally blunted or abolished the proliferative action of androgens but was not itself always inhibitory; in some experiments, stimulation of [3H]thymidine incorporation occurred. Collagen production, as assessed by [3H]proline incorporation into pepsin-resistant protein secreted by calvarial cells, was also stimulated by DHT. In some cultures, androgen responses were absent, although striking inhibitory responses to 1,25-(OH)2D3 were observed. These results illustrate complex patterns of responses to androgens and 1,25-(OH)2D3 in cells derived from rat bone.