Effects of androgens on parathyroid hormone and interleukin-1-stimulated prostaglandin production in cultured neonatal mouse calvariae

In this study we show direct inhibitory effects on prostaglandin E2 (PGE2) production by the androgens, testosterone (T) and dihydrotestosterone (DHT), in cultured neonatal mouse calvariae. After 24 h of preculture with or without androgens, bones were treated with bovine (1-34)-parathyroid hormone (PTH) or recombinant human interleukin-1 alpha (IL-1). During preculture androgens decreased PGE2 release only in those experiments in which control PGE2 was high. PTH increased medium PGE2 9-fold at 24 h, and 10(-11) M T inhibited this increase by 50%. Treatment with IL-1 for 24 h increased medium PGE2 19- to 22-fold, and 10(-10) M T and DHT inhibited this increase by 60 and 70%, respectively. T did not significantly affect the PTH-stimulated release of previously incorporated 45Ca or alter the PTH inhibition of incorporation of [3H]proline into collagenase-digestible protein. IL-1 stimulated 45Ca release by 60-80%, and small but significant reductions of 20-30% were seen with T and DHT. This study shows that T and DHT have direct effects on bone at physiologic concentrations, similar to our previous study in which PTH-stimulated PGE2 production in the same culture system was inhibited by physiologic concentrations of 17 beta-estradiol, and suggests that prostaglandins may mediate some of the effects of androgens in vivo.