Estrogen has rapid tissue-specific effects on rat bone

The decrease in cancellous bone formation after estrogen treatment is gener ally thought to be coupled with a prior decrease in bone resorption. To tes t the possibility that estrogen has rapid tissue-specific actions on bone m etabolism, we determined the time course (1-32 h) effects of diethylstilbes trol on steady-state mRNA levels for immediate-response genes, extracellula r matrix proteins, and signaling peptides in the proximal tibial metaphysis and uterus by using Northern blot and RNase protection assays. The regulat ion of signaling peptides by estrogen, although tissue specific, followed a similar time course in bone and uterus. The observed rapid decreases in ex pression of insulin-like growth factor I, a growth factor associated with b one formation; decreases in mRNA levels for bone matrix proteins; evidence for reduced bone matrix synthesis; failure to detect rapid increases in mRN A levels for signaling peptides implicated in mediating the inhibitory effe cts of estrogen on bone resorption (interleukin-1 and -6) as well as other cytokines that can increase bone resorption; and the comparatively long dur ation of the bone remodeling cycle in rats indicate that estrogen can decre ase bone formation by a mechanism that does not require a prior reduction i n bone resorption.