Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI

Microgravity causes rapid decrement in musculoskeletal mass is associated w ith a marked decrease in circulatory testosterone levels, as we reported in hindlimb-suspended (HLS) rats. In this model which simulates microgravity, we hypothesized that testosterone supplementation should prevent these los ses, and we tested this in two studies. Muscle volumes and bone masses were quantitated by using magnetic resonance imaging (MRI) on day 12. In the fi rst study, 12-wk-old Sprague-Dawley rats that were HLS for 12 days lost 28. 5% of muscle volume (53.3 +/- 4.8 vs. 74.5 +/- 3.6 cm(3) in the ground cont rol rats; P < 0.001) and had a 5% decrease in bone mineral density (BMD) (P < 0.05). In the second study, 30 male 12-wk-old Wistar rats were HLS and w ere administered either a vehicle (control), testosterone, or nandrolone de canoate (ND). An additional 20 rats were used as ground controls, one-half of which received testosterone. HLS rats had a significant reduction in mus cle volume (42.9 +/- 3.0 vs. 56 +/- 1.8 cm(3) in ground control rats; P < 0 .01). Both testosterone and ND treatments prevented this muscle loss (51.5 +/- 2 and 51.6 +/- 1.2 cm(3), respectively; a 63% improvement; P < 0.05). T here were no statistical differences between the two active treatment group s nor with the ground controls. Similarly, there was an 85% improvement:in BMD in the testosterone group (1.15 +/- 0.04 vs. 1.04 +/- 0.04 density unit s in vehicle controls; P < 0.05) and a 76% improvement in the ND group (1.1 3 +/- 0.07 density units), whereas ground control rats had a BMD of 1.17 +/ - 0.03 density units. Because serum testosterone levels are markedly reduce d in this model of simulated microgravity, androgen replacement seems to be a rational countermeasure to prevent microgravity-induced musculoskeletal losses.