Die Auswirkungen des selektiven Androgenrezeptor-Modulators Enobosarm auf die Skelettmuskulatur der orchiektomierten Ratte

The effects of the selective androgen receptor modulator Enobosarm on the skeletal muscle of the orchiectomized rat

by Johannes Valentin Boy Billy-Rubin Wolgast
Doctoral thesis
Date of Examination:2020-04-22
Date of issue:2020-03-23
Advisor:Prof. Dr. Wolfgang Brück
Referee:Prof. Dr. Stephan Sehmisch
Referee:Prof. Dr. Stephan von Haehling
Referee:Prof. Dr. Margarete Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-7924

 

 

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Abstract

English

Osteoporosis and sarcopenia are closely related diseases, which together affect our musculoskeletal system. Long researched as female diseases, the potential therapeutic effects of the selective androgen receptor modulator (SARMs) Enobosarm on the musculoskeletal system were now investigated using the osteoporotic model of the orchiectomized rat. This thesis deals exclusively with research on skeletal muscles. The experiment commenced with bilateral orchiectomy. After twelve weeks, all experimental animals underwent bilateral femoral osteotomy followed by stable plate osteosynthesis. After an additional six weeks, the animals were finally sacrificed to science. At the beginning of the experiment, 90 animals were divided into six groups: 1. (nonORX): non-orchiectomized; 2. (ORX): orchiectomized; 3. (SARMT): orchiectomized + Enobosarm, 0.4 mg/kg BW/d p.o., for the last six weeks; 4. (SARMP): orchiectomized + Enobosarm, 0.4 mg/kg BW/d p.o., for 18 weeks; 5. (TestT): orchiectomized + testosterone propionate, 46.67 mg/kg BW/d p.o., for the last six weeks; 6. (TestT): orchiectomized + testosterone propionate, 46.67 mg/kg BW/d p.o., for 18 weeks. The body weights of the test animals and the quantities of food consumed were recorded weekly. The Mm. longissimi, gastrocnemii and solei were histologically prepared post mortem and microscopically evaluated. The ratio of type 1 to type 2 muscle cells, the muscle cell cross-sectional surfaces and equatorial diameters as well as the capillary density were determined. The activity of creatine kinase in serum, the muscle weights, including M. levator ani, and prostate weights were also determined. Short-term treatment with Enobosarm and testosterone propionate (SARMT, TestT) tended to have beneficial effects on the skeletal muscles of the orchiectomized rat without significantly increasing the weight of the prostate. On the other hand, long-term therapy with Enobosarm (SARMP) led to increased prostate weights and did not have a clearly beneficial effect on skeletal muscles. For long-term applicability of Enobosarm, the application of lower doses should be investigated. Furthermore, a synergistic effect of substance and muscular training would be conceivable and should also be considered in the future.
Keywords: SARM; rat; muscle; Enobosarm; orchiectomy
Schlagwörter: SARM; Orchiektomie; Ratte; Enobosarm; Muskel
 
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