Alterations of Steroidogenesis by Exercise Countermeasures during Bed Rest
Investigators: Charles E. Wade, PhD, T. Peter Stein, PhD, and Janet C. L. Tou, PhD, NASA Ames Research Center, Moffett Field, California

Various countermeasures have been proposed to minimize some of the adverse effects of spaceflight. The end point for efficacy is usually the specific symptom of interest with little regard for confounding factors. Heavy exercise has been advocated as an effective countermeasure to attenuate loss of bone and muscle mass during spaceflight as well as to reduce the incidence of orthostatic intolerance upon return to Earth. The heavy exercise and increased demands (stress) during a spaceflight mission contribute to a shift in the steroidogenesis pathway away from the synthesis of testosterone and estrogen. However, the secondary effects of heavy daily exercise have not been investigated. One of the primary effects of over training is a reduction in testosterone in males and a decrease in estrogen in females. These hormones have been implicated in the maintenance of normal bone and muscle health. Research performed during this investigation included a detailed reproductive history and recording of the reproductive cycle in females. Urine samples were collected for the measurement of aldosterone, cortisol, progesterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), total testosterone, free testosterone, estradiol and creatinine. Blood samples were collected for the determination of corticosterone, estradiol, and testosterone. This investigation studied the potential reductions in testosterone and estrogen during the use of heavy exercise countermeasures and was conducted in bed rest campaigns both at UTMB and in Toulouse, France

Bed Rest and Immunity
Investigators: Gerald Sonnenfeld, PhD, Janet Butel, and David Niesel, PhD, Morehouse School of Medicine, Atlanta, Georgia

One of the important regulatory biology interactions affected by spaceflight is the regulation of the immune response. Alterations in the regulation of immunity could have profound effects on the ability of humans to resist infection and development of tumors. Studies on the immune system have been carried out on cell cultures, animals, and humans in space and in environments that model some spaceflight conditions. Limited immunologic studies have been carried out on crew members who have flown in space. Those studies have shown an inhibition of mitogen-induced proliferation of lymphocytes obtained from astronauts and cosmonauts involved in a wide variety of spaceflight missions, including the Apollo-Soyuz Test Project, Skylab, Space Shuttle, and various Russian flights. Samples taken from crew members as late as 7 days postflight indicated that the lymphocyte proliferative response had not returned to normal.

In cell populations obtained from crews immediately after return from space, the following results were observed: (1) alterations in leukocyte subset distribution and (2) alterations in interferon and other cytokine production and alterations in natural killer cell activity. One immunologic parameter that has been determined during spaceflight is delayed hypersensitivity skin test responses to common recall antigens. These responses were found to be inhibited during both short- and long-term spaceflights. Delayed-type hypersensitivity skin tests are simple measures for cellular immune function, such as the standard skin test for tuberculosis. Astronauts who have flown on the Space Shuttle have shown increased urinary catecholamine excretion and reactivation of Epstein-Barr virus. Exposure to spaceflight could have led to alterations in immune responses that allowed reactivation of latent viruses. This observation raises a concern with respect to susceptibility of spaceflight crew members to cancer. Herpes viruses have been found to be associated with non-Hodgkin's lymphoma tumors. Therefore, reactivation of persistent viruses in space raises concerns that there may be some association of the virus with future tumor development.

During this study, saliva, blood, and urine samples were collected to determine the cellular immune responses of subjects during 6-degree head-down-tilt bed rest. Measurements included pro-IFN-y, IL-12, anti-IL-10, IL-1RA, leukocyte proliferation, and T-helper T cells. Samples were also analyzed for reactivation of Herpes virus and polyomaviruses.

Based on the preliminary results from Campaign 1, the physiologic changes shown by the subjects participating in this study were similar to the changes observed in humans exposed to spaceflight. The bed rest design employed during this campaign appeared to provide an excellent ground-based model to study the varied physiologic changes. The data collected from the 3 subjects in this campaign will be combined with data from additional subjects and serve as control data for the evaluation and assessment of potential countermeasures. Future campaigns have been extended to 90 days of 6-degree head-down-tilt bed rest which should enhance the physiologic changes and allow a more complete comparison with flight results and countermeasure evaluations.

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