We sought to determine if androgen administration to orchiectomized (ORX) rats affects ribosome biogenesis markers. Ten month-old male Fischer 344 rats (n=10-11/group) were treated for 4 weeks following 2 weeks after ORX/Sham surgery with either: a) ORX + testosterone enanthate (ORX+Test; 7 mg/wk), or b) ORX + trenbolone enanthate (ORX+Tren; 1 mg/wk), a non-5α-reducible, non-aromatizable synthetic testosterone analogue. LABC muscle was removed during necropsy and genes of interest were analyzed using RT-PCR. A trend towards significance existed between groups regarding total RNA/mg wet muscle (p = 0.098), with ORX being 20-23% lower versus other groups. Interestingly, several ribosomal biogenesis markers were greater in SHAM versus other groups (p < 0.001). 5S rRNA and Raptor mRNA were greater in ORX+Tren versus other groups, respectively (p < 0.05). Rpl-3 mRNA was greater in ORX and ORX+Tren versus SHAM (p = 0.048, 0.002), and was also greater in ORX+Test (p < 0.001, 0.02) versus SHAM and ORX. Nucleophosmin mRNA was greater in ORX versus other groups (p < 0.001). ORX suppressed the expression of various ribosomal markers and genes, though androgen treatment largely rescued this effect.

more than just a role in energy balance 28 Sleep disturbance alters autonomic balance to the heart 30 The mighty protein: Insulin-like growth factor type 1 34 Secrets of life from beyond the grave

Previous research has demonstrated that blood flow restriction during low intensity resistance exercise (BFR-Low) results in a potent muscle growth response in humans. However, it is unclear whether this stimulus is similar to that provoked with free-flow high intensity resistance exercise (FF-HI). PURPOSE: To determine the acute growth hormone (GH) and insulin-like growth factor (IGF-1) responses to BFR-Low and FF-HI in young adults. Additionally, because BFR may induce adverse reactions we evaluated cardiovascular, endothelial inflammation with vascular cell adhesion molecule (VCAM) and blood coagulation (D-dimer) responses. METHODS: Ten healthy subjects aged 20-39 years reported to the laboratory between 7 and 9 AM on two separate occasions in a fasted condition. Knee extension exercise was performed at 20% of maximal strength for the BFR-Low condition in comparison to a FF-HI performed at 80% of maximal strength. Both conditions were performed for 5 sets until task failure. During BFR-Low exercise, a 10 cm wide tourniquet cuff was placed around the upper thigh at 1.5 systolic blood pressure immediately before exercise and remained inflated (∼15 minutes). Blood was sampled every 10 minutes for 150 minutes to assess GH responses and IGF-1 was measured at baseline and 90 minutes post-exercise. RESULTS: Subjects demonstrated a greater mean increase in GH levels with BFR-Low exercise (2.1 ± 2.1 ng/ml) when compared to FF-HI (1.5 ± 2.6 ng/ml), but this difference was not statistically different (p = 0.61). IGF-1 levels demonstrated no change regardless of the exercise condition. Peak heart rate (HR) and systolic blood pressure (BP) showed similar responses to both conditions (HR: BFR-Low: 83.8 ± 12.4; FF-HI: 84.8 ± 6.7 bpm) (SBP: BFR-Low: 148.8 ± -.9 vs. FF-HI: 139.0 ± 15.6 mmHg). Peak diastolic blood pressure was elevated to a greater extent during BFR-Low exercise (BFR-Low: 103 ± 9.7; FF-HI: 92.6 ± 12.4, p=0.05). D-dimer, a degradation product of crosslinked fibrin and VCAM levels showed no change 30 min post exercise for either condition. CONCLUSIONS: Resistance exercise performed at low intensity with BFR has a similar systemic acute growth, blood coagulation and endothelial inflammatory response, but greater cardiovascular demand when compared to resistance exercise performed at a high intensity.

PURPOSE: Insulin-like growth factor I (IGF-I) is a potent myogenic factor that has been shown to play a critical role in muscle regeneration and muscle hypertrophy. The purpose of this study was to evaluate the effect of IGF-I overexpression during cast immobilization and further examine the recovery of muscle size and function during reambulation. METHODS: The anterior compartment of the left hindlimb of young adult (3 weeks) C57BL6 mice were injected with a recombinant adeno-associated virus vector for IGF-I (rAAV-IGF-I). At 20 weeks of age, mice were cast immobilized for 2 weeks. The tibialis anterior (TA) and extensor longus digitorum (EDL) muscles were removed from both legs after 2 wks of cast immobilization and after 1 and 3 weeks of free cage reambulation. RESULTS: Dramatic increases in IGF-I mRNA and protein levels with IGF-I overexpression were associated with significant increases in muscle wet weight and tetanic force. Enhanced muscle regenerations were shown by increased expressions of central nuclei, embryonic myosin and Pax7 positive fibers after 1 week of reambulation in IGF-I overexpression muslces. CONCLUSIONS: Local overexpression of IGF-I in skeletal muscle results in more muscle regenerations after 1 week of reambulation and maintains the muscle mass and strength advantage present at baseline during unloading and reloading conditions.

Reloading following cast immobilization induces significant muscle damage in the postural soleus muscle. Reloading injury is associated with muscle remodeling and triggers muscle regeneration. Insulin-like growth factor-I (IGF-I) is a potent myogenic factor and has been shown to play an important role in mediating muscle plasticity in response to alterations in loading. PURPOSE: To study the effect of 2 weeks of cast immobilization and 1 week of limb reloading on IGF-I protein levels in the postural mouse soleus muscle. METHODS: At 18 weeks of age, sixteen female C57BL6 mice (weight 21.61±0.19g) were randomly divided into 3 groups: control (n=5); cast immobilization + 0 days reambulation (n=5); cast immobilization + 1 week reambulation (n=6). Both hindlimbs were immobilized with the knees extended 115°∼120°of plantarflexion to maximize atrophy in the soleus muscle. After cast immobilization, the soleus muscles were removed and muscle wet weights were determined. The IGF-I protein content was quantified using a mouse IGF-I immunoassay. RESULTS: Two weeks of cast immobilization resulted in a 22% decrease in soleus muscle wet weight (7.16±0.14mg vs. 5.59±0. 11mg), but did not significantly alter the IGF-I protein content. In contrast, 1 week of reambulation induced a 3.7 fold increase in the soleus IGF-I protein content (12.58 ± 1.44ng/g) compared to both control (3.14 ±0.17ng/g) and cast immobilized muscles (3.16 ± 0.27ng/g) (P<0.01). CONCLUSION: IGF-I protein levels in mice soleus muscle were markedly elevated during reambulation following 2 weeks of cast immobilization. Our findings suggest that IGF-I may play a critical role in mediating muscle regeneration during reambulation following immobilization/disuse.