High Concentrations of 17β-Estradiol Stimulate Trabecular Bone Formation in Adult Female Rats*

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Abstract
Although the effects of low concentrations of 17β-estradiol (E2) on bone formation and resorption are well described, little is known of the effects of E2 on bone at concentrations that circulate during pregnancy. We, therefore, investigated the effects of administration of high dose E2 to 3-monthold female Wistar rats on biochemical and histomorphometric indices of bone formation and resorption. Animals receiving exogenous E2 (4 mg/kg-day for 17 days; n = 9) showed a mean serum E2 concentration of 17.5 ± 2.9 nM, compared with 0.6 ± 0.2 nM in those receiving vehicle alone (n = 10). The bone formation rate, measured at the proximal tibial metaphysis after the administration of double fluorochrome labels, was greatly increased in the E2 group (13.6 ± 2.0 × 10-2 μm3/μm2 · day) compared to controls (3.9 ± 0.9), as was serum alkaline phosphatase (E2, 133.6 ± 10.1 IU; controls, 87.5 ± 5.5). This increase in the rate of bone formation was associated with a significant increase in trabecular bone volume. E2 treatment did not affect urinary hydroxyproline excretion or histomorphometric indices of bone resorption. These findings suggest that high concentrations of E2 strongly stimulate the formation of trabecular bone. This may represent an important mechanism by which calcium stores are accumulated during pregnancy in rats, in anticipation of the mineral requirements of lactation. (Endocrinology128: 408–412, 1991)

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