Introduction: The contribution of reduced testosterone levels to tail suspension (TS)-induced muscle atrophy remains equivocal. The molecular mechanism by which testosterone regulates muscle mass during TS has not been investigated. Methods: Effects of TS on serum testosterone levels, muscle mass, and expression of muscle atrophy- and hypertrophy-inducing targets were measured in soleus (SOL) and extensor digitorum longus (EDL) muscles after testosterone administration during 1, 5, and 14 days of TS in male mice. Results: TS produced an increase followed by a transient drop in testosterone levels. Muscle atrophy was associated with downregulation of Igf1 and upregulation of Mstn, Redd1, Atrogin-1, and MuRF1 mRNA with clear differences in Igf1, Mstn, and MAFbx/Atrogin-1 gene expression between SOL and EDL. Testosterone supplementation did not affect muscle mass or protein expression levels during TS. Conclusions The known anabolic effects of testosterone are not sufficient to ameliorate loss of muscle mass during TS
CLARK BRIAN C., In Vivo Alterations in Skeletal Muscle Form and Function after Disuse Atrophy : , 10.1249/mss.0b013e3181a645a6
Kamiya Hiroyuki, Sasaki Shoichi, Ikeuchi Takahito, Umemoto Yukihiro, Tatsura Hiroyuki, Hayashi Yutaro, Kaneko Shigeo, Kohri Kenjiro, Effect of Simulated Microgravity on Testosterone and Sperm Motility in Mice, 10.1002/j.1939-4640.2003.tb03140.x
Wimalawansa Sunishka M., Wimalawansa Sunil J., Simulated weightlessness-induced attenuation of testosterone production may be responsible for bone loss, 10.1007/bf02738624
Royland Joyce E., Weber L.J., Fitzpatrick M., Testes size and testosterone levels in a model for weightlessness, 10.1016/0024-3205(94)90005-1
Tash Joseph S., Johnson Donald C., Enders George C., Long-term (6-wk) hindlimb suspension inhibits spermatogenesis in adult male rats, 10.1152/japplphysiol.00931.2001
Hadley, J Appl Physiol, 72, 748 (1992)
DEMURA R., SUZUKI T., NAKAMURA S., KOMATU H., ODAGIRI E., DEMURA H., Effect of Immobilization Stress on Testosterone and Inhibin in Male Rats, 10.1002/j.1939-4640.1989.tb00089.x
Bhasin, J Clin Endocrinol Metab, 82, 407 (1997)
Wimalawansa, J Appl Physiol, 86, 1841 (1999)
Tsika, J Appl Physiol, 63, 2128 (1987)
Joumaa W. H., Bouhlel A., Bigard X., Leoty C., Nandrolone decanoate pre-treatment attenuates unweighting-induced functional changes in rat soleus muscle, 10.1046/j.1365-201x.2002.01035.x
Hoffman Eric P, Nader Gustavo A, Balancing muscle hypertrophy and atrophy, 10.1038/nm0604-584
Bodine Sue C., Stitt Trevor N., Gonzalez Michael, Kline William O., Stover Gretchen L., Bauerlein Roy, Zlotchenko Elizabeth, Scrimgeour Angus, Lawrence John C., Glass David J., Yancopoulos George D., 10.1038/ncb1101-1014
Yin Hui-Nan, Chai Jia-Ke, Yu Yong-Ming, Shen Chuan-An, Wu Yan-Qiu, Yao Yong-Ming, Liu Hui, Liang Li-Ming, Tompkins Ronald G., Sheng Zhi-Yong, Regulation of Signaling Pathways Downstream of IGF-I/Insulin by Androgen in Skeletal Muscle of Glucocorticoid-Treated Rats : , 10.1097/ta.0b013e31817e7420
Haren M. T., Siddiqui A. M., Armbrecht H. J., Kevorkian R. T., Kim M. J., Haas M. J., Mazza A., Kumar Vijaya B., Green M., Banks W. A., Morley J. E., Testosterone modulates gene expression pathways regulating nutrient accumulation, glucose metabolism and protein turnover in mouse skeletal muscle : Testosterone and muscle gene expression, 10.1111/j.1365-2605.2010.01061.x
White James P., Gao Song, Puppa Melissa J., Sato Shuichi, Welle Stephen L., Carson James A., Testosterone regulation of Akt/mTORC1/FoxO3a signaling in skeletal muscle, 10.1016/j.mce.2012.10.019
Sandri Marco, Sandri Claudia, Gilbert Alex, Skurk Carsten, Calabria Elisa, Picard Anne, Walsh Kenneth, Schiaffino Stefano, Lecker Stewart H, Goldberg Alfred L, Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy, 10.1016/s0092-8674(04)00400-3
Stitt Trevor N., Drujan Doreen, Clarke Brian A., Panaro Frank, Timofeyva Yekatarina, Kline William O., Gonzalez Michael, Yancopoulos George D., Glass David J., The IGF-1/PI3K/Akt Pathway Prevents Expression of Muscle Atrophy-Induced Ubiquitin Ligases by Inhibiting FOXO Transcription Factors, 10.1016/s1097-2765(04)00211-4
Bodine S. C., Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy, 10.1126/science.1065874
Gomes M. D., Lecker S. H., Jagoe R. T., Navon A., Goldberg A. L., Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy, 10.1073/pnas.251541198
Ibebunjo C., Eash J. K., Li C., Ma Q., Glass D. J., Voluntary running, skeletal muscle gene expression, and signaling inversely regulated by orchidectomy and testosterone replacement, 10.1152/ajpendo.00402.2010
Pires-Oliveira M., Maragno A. L. G. C., Parreiras-e-Silva L. T., Chiavegatti T., Gomes M. D., Godinho R. O., Testosterone represses ubiquitin ligases atrogin-1 and Murf-1 expression in an androgen-sensitive rat skeletal muscle in vivo, 10.1152/japplphysiol.00490.2009
Trendelenburg A. U., Meyer A., Rohner D., Boyle J., Hatakeyama S., Glass D. J., Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size, 10.1152/ajpcell.00105.2009
Carlson, Am J Physiol, 277, R601 (1999)
Wehling, FASEB J, 14, 103 (2000)
Jones, FASEB J, 18, 1025 (2004)
Chen Yi-Wen, Gregory Chris M., Scarborough Mark T., Shi Rongye, Walter Glenn A., Vandenborne Krista, Transcriptional pathways associated with skeletal muscle disuse atrophy in humans, 10.1152/physiolgenomics.00115.2006
Diel P., Friedel A., Geyer H., Kamber M., Laudenbach-Leschowsky U., Schänzer W., Schleipen B., Thevis M., Vollmer G., Zierau O., The prohormone 19-norandrostenedione displays selective androgen receptor modulator (SARM) like properties after subcutaneous administration, 10.1016/j.toxlet.2008.01.014
Mendler Luca, Baka Zsuzsanna, Kovács-Simon Andrea, Dux László, Androgens negatively regulate myostatin expression in an androgen-dependent skeletal muscle, 10.1016/j.bbrc.2007.07.023
Brugarolas J., Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex, 10.1101/gad.1256804
Kelleher A. R., Kimball S. R., Dennis M. D., Schilder R. J., Jefferson L. S., The mTORC1 signaling repressors REDD1/2 are rapidly induced and activation of p70S6K1 by leucine is defective in skeletal muscle of an immobilized rat hindlimb, 10.1152/ajpendo.00409.2012
Wu Yong, Zhao Weidong, Zhao Jingbo, Zhang Yuanfei, Qin Weiping, Pan Jiangping, Bauman William A., Blitzer Robert D., Cardozo Christopher, REDD1 Is a Major Target of Testosterone Action in Preventing Dexamethasone-Induced Muscle Loss, 10.1210/en.2009-0530
Jänne, Endocrinology, 140, 4166 (1999)
Taieb J., Testosterone Measured by 10 Immunoassays and by Isotope-Dilution Gas Chromatography-Mass Spectrometry in Sera from 116 Men, Women, and Children, 10.1373/49.8.1381
McNamara K.M., Harwood D.T., Simanainen U., Walters K.A., Jimenez M., Handelsman D.J., Measurement of sex steroids in murine blood and reproductive tissues by liquid chromatography–tandem mass spectrometry, 10.1016/j.jsbmb.2010.02.001
Glass David, Roubenoff Ronenn, Recent advances in the biology and therapy of muscle wasting : Glass & Roubenoff, 10.1111/j.1749-6632.2010.05809.x
Okamoto Takeshi, Torii Suguru, Machida Shuichi, Differential gene expression of muscle-specific ubiquitin ligase MAFbx/Atrogin-1 and MuRF1 in response to immobilization-induced atrophy of slow-twitch and fast-twitch muscles, 10.1007/s12576-011-0175-6
Axell A.-M., Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice, 10.1152/ajpendo.00058.2006
Vanderschueren, Endocrinology, 141, 1642 (2000)
Fiers Tom, Casetta Bruno, Bernaert Brigitte, Vandersypt Eric, Debock Martine, Kaufman Jean-Marc, Development of a highly sensitive method for the quantification of estrone and estradiol in serum by liquid chromatography tandem mass spectrometry without derivatization, 10.1016/j.jchromb.2012.02.034
Vandesompele Jo, De Preter Katleen, Pattyn Filip, Poppe Bruce, Van Roy Nadine, De Paepe Anne, Speleman Frank, 10.1186/gb-2002-3-7-research0034
Wallace Marita A., Hock M. Benjamin, Hazen Bethany C., Kralli Anastasia, Snow Rod J., Russell Aaron P., Striated muscle activator of Rho signalling (STARS) is a PGC-1α/oestrogen-related receptor-α target gene and is upregulated in human skeletal muscle after endurance exercise : STARS is upregulated by endurance exercise, 10.1113/jphysiol.2011.205468
Wheeler G, Cumming D, Burnham R, Maclean I, Sloley B D, Bhambhani Y, Steadward R D, Testosterone, cortisol and catecholamine responses to exercise stress and autonomic dysreflexia in elite quadriplegic athletes, 10.1038/sc.1994.51
Lennartsson Anna-Karin, Kushnir Mark M., Bergquist Jonas, Billig Håkan, Jonsdottir Ingibjörg H., Sex steroid levels temporarily increase in response to acute psychosocial stress in healthy men and women, 10.1016/j.ijpsycho.2012.03.001
SAPOLSKY ROBERT M., Stress-Induced Suppression of Testicular Function in the Wild Baboon: Role of Glucocorticoids*, 10.1210/endo-116-6-2273
Gardetto, J Appl Physiol, 66, 2739 (1989)
Miokovic T., Armbrecht G., Felsenberg D., Belavy D. L., Heterogeneous atrophy occurs within individual lower limb muscles during 60 days of bed rest, 10.1152/japplphysiol.00611.2012
Svensson J., Moverare-Skrtic S., Windahl S., Swanson C., Sjogren K., Stimulation of both estrogen and androgen receptors maintains skeletal muscle mass in gonadectomized male mice but mainly via different pathways, 10.1677/jme-09-0165
Ahtiainen Juha P., Hulmi Juha J., Kraemer William J., Lehti Maarit, Nyman Kai, Selänne Harri, Alen Markku, Pakarinen Arto, Komulainen Jyrki, Kovanen Vuokko, Mero Antti A., Häkkinen Keijo, Heavy resistance exercise training and skeletal muscle androgen receptor expression in younger and older men, 10.1016/j.steroids.2010.10.012
Awede Bonaventure, Thissen Jean-Paul, Gailly Phillipe, Lebacq Jean, Regulation of IGF-I, IGFBP-4 and IGFBP-5 gene expression by loading in mouse skeletal muscle, 10.1016/s0014-5793(99)01469-6
Hanson Andrea M., Harrison Brooke C., Young Mary H., Stodieck Louis S., Ferguson Virginia L., Longitudinal characterization of functional, morphologic, and biochemical adaptations in mouse skeletal muscle with hindlimb suspension : Characterization of Hindlimb Suspension, 10.1002/mus.23753
Sugiura T., Changes in PKB/Akt and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading, 10.1152/ajpregu.00688.2004
Childs T. E., Spangenburg E. E., Vyas D. R., Booth F. W., Temporal alterations in protein signaling cascades during recovery from muscle atrophy, 10.1152/ajpcell.00478.2002
LAWLER JOHN M., KWAK HYO-BUM, KIM JONG-HEE, LEE YANG, HORD JEFFREY M., MARTINEZ DANIEL A., Biphasic Stress Response in the Soleus during Reloading after Hind Limb Unloading : , 10.1249/mss.0b013e31823ab37a
Dupont E., Cieniewski-Bernard C., Bastide B., Stevens L., Electrostimulation during hindlimb unloading modulates PI3K-AKT downstream targets without preventing soleus atrophy and restores slow phenotype through ERK, 10.1152/ajpregu.00793.2009
Gustafsson T., Osterlund T., Flanagan J. N., von Walden F., Trappe T. A., Linnehan R. M., Tesch P. A., Effects of 3 days unloading on molecular regulators of muscle size in humans, 10.1152/japplphysiol.00110.2009
Reich K. A., Chen Y.-W., Thompson P. D., Hoffman E. P., Clarkson P. M., Forty-eight hours of unloading and 24 h of reloading lead to changes in global gene expression patterns related to ubiquitination and oxidative stress in humans, 10.1152/japplphysiol.00444.2010
Krawiec B. J., Hindlimb casting decreases muscle mass in part by proteasome-dependent proteolysis but independent of protein synthesis, 10.1152/ajpendo.00126.2005
Maki Taiki, Yamamoto Daisuke, Nakanishi Shiho, Iida Keiji, Iguchi Genzo, Takahashi Yutaka, Kaji Hidesuke, Chihara Kazuo, Okimura Yasuhiko, Branched-chain amino acids reduce hindlimb suspension-induced muscle atrophy and protein levels of atrogin-1 and MuRF1 in rats, 10.1016/j.nutres.2012.07.005
Labeit Siegfried, Kohl Christine H., Witt Christian C., Labeit Dittmar, Jung Jeong, Granzier Henk, Modulation of Muscle Atrophy, Fatigue and MLC Phosphorylation by MuRF1 as Indicated by Hindlimb Suspension Studies on MuRF1-KO Mice, 10.1155/2010/693741
Drummond Micah J., Glynn Erin L., Lujan Heidi L., Dicarlo Stephen E., Rasmussen Blake B., Gene and protein expression associated with protein synthesis and breakdown in paraplegic skeletal muscle, 10.1002/mus.20976
Salanova M., Schiffl G., Püttmann B., Schoser B. G., Blottner D., Molecular biomarkers monitoring human skeletal muscle fibres and microvasculature following long-term bed rest with and without countermeasures, 10.1111/j.1469-7580.2008.00854.x
Chen Guoan, Gharib Tarek G., Huang Chiang-Ching, Taylor Jeremy M. G., Misek David E., Kardia Sharon L. R., Giordano Thomas J., Iannettoni Mark D., Orringer Mark B., Hanash Samir M., Beer David G., Discordant Protein and mRNA Expression in Lung Adenocarcinomas, 10.1074/mcp.m200008-mcp200
Lichtinghagen Ralf, Musholt Petra B, Lein Michael, Römer Andreas, Rudolph Birgit, Kristiansen Glen, Hauptmann Steffen, Schnorr Dietmar, Loening Stefan A, Jung Klaus, Different mRNA and Protein Expression of Matrix Metalloproteinases 2 and 9 and Tissue Inhibitor of Metalloproteinases 1 in Benign and Malignant Prostate Tissue, 10.1016/s0302-2838(02)00324-x
Lee S.-J., McPherron A. C., Regulation of myostatin activity and muscle growth, 10.1073/pnas.151270098
Chen S. N., Czernuszewicz G., Tan Y., Lombardi R., Jin J., Willerson J. T., Marian A. J., Human Molecular Genetic and Functional Studies Identify TRIM63, Encoding Muscle RING Finger Protein 1, as a Novel Gene for Human Hypertrophic Cardiomyopathy, 10.1161/circresaha.112.270207
Bibliographic reference
De Naeyer, Hélène ; Lamon, Séverine ; Russell, Aaron P ; Everaert, Inge ; De Spaey, Annelies ; et. al. Effects of tail suspension on serum testosterone and molecular targets regulating muscle mass. In: Muscle & Nerve, Vol. 52, no.2, p. 278-288 (2015)