title: Simulated weightlessness-induced attenuation of testosterone production may be responsible for bone loss.
abstract: This study examined the effects of simulated weightlessness on serum hormone levels and their relationship to bone mineral density (BMD). The tail-suspended (i.e., hindlimb suspended, HLS) rat model was used to simulate weightless conditions through hindlimb unloading to assess changes in hormonal profile and the associated bone loss. In the first study, 24 adult male rats were assigned to two groups with 12 rats being HLS for 12 d, and the remaining 12 rats serving as ground controls. On d 0, 6, and 12, blood samples were taken to estimate circulating hormone levels. HLS rats had significant reductions in testosterone, 1,25 (OH)2 vitamin D, and thyroxine levels by d 6 (p<0.01); their testosterone levels were almost undetectable by d 12 (p<0.001). Serum cortisol levels in these rats were elevated on d 6 (p<0.02), but returned to normal levels by d 12. No changes were observed with serum ionized calcium and other hormones examined, as well as the body weights, and weights of thymus, heart, and brain. In the second study, eight rats were ground controls, while an additional eight rats were HLS for 12 d before being removed from tail-suspension and maintained for a further 30 d. Blood samples were collected every 6th d for 42 d. This study showed that both serum thyroxine and 1,25(OH)2 vitamin D levels returned to normal levels soon after hind limb unweighting, while serum testosterone levels matched normal levels only after a further 3-4 wk. These studies showed a significant decrease of femur weights, but not weights of humeri in HLS rats suggesting that this is a specific effect on unloaded bones. On d 12 in both studies, a significant reduction in the lumbar spine (p<0.05) and the femoral neck (p<0.01) BMD appeared in HLS rats. This was confirmed in the second study, where HLS led to a significant decrease in BMD even extending to d 42. Previous studies have shown that space flight and tail-suspension lead to marked reductions in bone formation with little effect on bone resorption. Recently, we reported that androgen replacement can indeed prevent bone losses in this animal model. Therefore, it seems logical to propose that the significant decreases of serum testosterone observed in these tail-suspended animals are, at least in part, responsible for the losses of BMD seen in their affected weight-bearing bones (i.e., lumbar spine and the femur). Considering that 1. testosterone is anabolic to osteoblasts and also decreases the rate of bone turnover 2. serum testosterone levels are markedly suppressed in simulated weightlessness, and 3. testosterone replacement therapy prevented the bone loss in HLS rats, we propose that the testosterone deficiency in this animal model is related to their bone loss.
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston 77555-1065, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Wimalawansa
authors.forename: S J
authors.initials: SJ
authors.lastname: Wimalawansa
mesh_terms: D000818:Animals; D015519:Bone Density; D002117:Calcitriol / Q000097:blood; D003345:Corticosterone / Q000097:blood; D005269:Femur / Q000033:anatomy & histology; D006614:Hindlimb; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009929:Organ Size; D010024:Osteoporosis / Q000209:etiology*; D011187:Posture; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000096:biosynthesis* / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014893:Weightlessness / Q000009:adverse effects*
chemical_list: D013739:Testosterone; D002117:Calcitriol; D013974:Thyroxine; D003345:Corticosterone; D006854:Hydrocortisone