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

Abstract

J. Wimalawansa. Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI. J. Appl. Physiol. 86(6): 1841-1846, 1999.-Microgravity causes rapid decrement in musculoskeletal mass is associated with 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 losses, 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 first study, 12-wk-old Sprague-Dawley rats that were HLS for 12 days lost 28.5% of muscle volume (53.3 Ϯ 4.8 vs. 74.5 Ϯ 3.6 cm 3 in the ground control rats; P Ͻ 0.001) and had a 5% decrease in bone mineral density (BMD) (P Ͻ 0.05). In the second study, 30 male 12-wk-old Wistar rats were HLS and were administered either a vehicle (control), testosterone, or nandrolone decanoate (ND). An additional 20 rats were used as ground controls, one-half of which received testosterone. HLS rats had a significant reduction in muscle volume (42.9 Ϯ 3.0 vs. 56 Ϯ 1.8 cm 3 in ground control rats; P Ͻ 0.01). Both testosterone and ND treatments prevented this muscle loss (51.5 Ϯ 2 and 51.6 Ϯ 1.2 cm 3 , respectively; a 63% improvement; P Ͻ 0.05). There were no statistical differences between the two active treatment groups nor with the ground controls. Similarly, there was an 85% improvement in BMD in the testosterone group (1.15 Ϯ 0.04 vs. 1.04 Ϯ 0.04 density units in vehicle controls; P Ͻ 0.05) and a 76% improvement in the ND group (1.13 Ϯ 0.07 density units), whereas ground control rats had a BMD of 1.17 Ϯ 0.03 density units. Because serum testosterone levels are markedly reduced in this model of simulated microgravity, androgen replacement seems to be a rational countermeasure to prevent microgravity-induced musculoskeletal losses. osteoporosis; microgravity; bone turnover; bone mineral density; anabolic steriod; disuse atrophy DECREMENTS IN BONE AND MUSCLE mass are major concerns in extended space missions (1,8,9,38,49). Immobilization (e.g., bed rest or restricted movements of limbs) can also cause rapid losses in muscle or bone mass (6,9,25,26). Immobilization, prolonged bed rest, and spaceflight conditions inducing microgravity conditions can lead to the general or selective loss of muscle volume and mass. In addition, these conditions lead to negative calcium balance and loss of bone mineral density (BMD) (11,13,32,33). A similar reduction in musculoskeletal mass has been reported due to the immobilization of extremities seen in external bandaging, casting, or neural resectioning (13,25,27,(39)(40)(41)(42)(43). Both mineralization and collagen metabolism seem to be impaired in animals during the first few days of spaceflight (34). Urine analysis in Skylab astronauts has shown a significant loss of minerals, including calcium (10, 37). Reduction of muscle forces leads to a decrease in bone formation and BMD in the os calcis and an i...

Overload-induced androgen receptor expression in the aged rat hindlimb receiving nandrolone decanoate

“…The regulation of skeletal muscle mass by anabolic steroidinduced cellular signaling and the potential for interactions with mechanical signaling pathways have not been well defined. Studies examining exogenous testosterone administration's effect on young rat skeletal muscle mass have reported mixed results, and even less is understood about targets of altered gene expression (1,7,45,48). Differences in results between studies are likely due to drug type, dosage, and administration schedules.…”

“…The anabolic steroid nandrolone decanoate (Deca-Durabolin, Oranon) was used in these studies because of its long biological half-life and because previous studies have demonstrated an anabolic effect in rat skeletal muscle (12). The selected dose of nandrolone decanoate administration has been previously demonstrated to prevent hindlimb suspension-induced rat skeletal muscle atrophy (48). Nandrolone decanoate was injected (6 mg/kg body wt) intramuscularly into the hip region every 7 days, and the right and left hip region alternated each week.…”

“…A synergistic relationship between testosterone and muscle loading is present in functionally overloaded rat muscle subject to disuse atrophy (45). Anabolic steroid administration can also abolish unloaded atrophy in the rat quadriceps muscle (48). Although anabolic steroids are a potent skeletal muscle mass effector, the intracellular signaling mechanisms induced by the interaction of overload and anabolic steroids have not been demonstrated.…”

The effect of microgravity on tissue structure and function of rat testis

“…In recent years, a specific role of androgens in skeletal homeostasis has been proposed (37). Studies have shown that androgens may protect men against osteoporosis via the maintenance of expansion of cortical bone (38). Therefore, the effect on the expression of androgens caused by damage to the structure and function of testicular tissue in a microgravity environment may reflect on decrements in bone and muscle mass.…”

Androgens Up-regulate Transcription of the Notch Inhibitor Numb in C2C12 Myoblasts via Wnt/β-Catenin Signaling to T Cell Factor Elements in the Numb Promoter

“…Administration of testosterone promotes the differentiation of mesenchymal stem cells into the myogenic lineage (22). Testosterone is able to increase skeletal muscle mass and strength in elderly men and in many conditions resulting in muscle atrophy, such as cancer and burn-induced cachexia (23), microgravity (24), immobilization (25), and spinal cord injury (26). The precise mechanisms underlying these actions of androgens, however, are poorly understood.…”