The dominant negative activity of GRβ resides within its unique carboxyl-terminal 15 amino acids (217). Atrogenes include transcription factor FOXO, a major switch for the stimulation of several atrogenes, and two ubiquitin ligases atrogin-1 and MuRF-1, involved in the targeting of protein to be degraded by the proteasome machinery, and LC3 (186, 201, 209, 210). The catabolic actions of cortisol resulting in muscle proteolysis occur largely via the ubiquitin–proteasome and lysosomal systems (186, 209–211). Mechanistically, the selective increase in GRβ appears to involve the splicing factor SRp30c (serine/arginine-rich protein p30c) (202, 203).
Of importance is the response of IGFBPs which have generated more consistent responses with resistance exercise acutely elevating IGFBP-3 (21). Looking at the IGFBPs has provide a more fruitful area of study as they have shown a more reliable pattern of responses to acute resistance exercise protocols. However, there is little doubt, IGF-I is a primary player in anabolic signaling targeted to many tissues, including skeletal muscle. This was demonstrated with resistance exercise in men and women in two studies by Kraemer's research groups (144, 145) where the short rest workouts using 1 min between sets and exercises demonstrated the highest blood lactate responses and IGH responses. The mere differences in receptor binding between bio and immune assays and their differential signaling raise questions as to their acute and chronic roles in exercise stress and adaptations. But most important exercise-induced changes in GH bioactivity were experienced after 6 months of training (6 × 10 squat at 80% of 1 RM with 2 min rest between sets). We believe this interesting result reflects the importance of either di-sulfide linked GH aggregates, and/or GH bound to GH-binding protein, for generation of somatogenic activity.
The principal androgen, testosterone, is an anabolic-androgenic steroid hormone which is synthesized from cholesterol—produced mainly in Leydig cells in men, and the ovary (25%) and adrenalzona fasciculata (25%) in women, via conversion from progesterone, with the remaining ~50% being produced from circulating androstenedione (Burger, 2002). RE induces marked anabolic hormone responses, in particular those involving testosterone, growth hormone (GH) and IGF-1 (Spiering et al., 2008). Even today after significant efforts to develop pharmaceutical strategies to mitigate muscle wasting (Sepulveda et al., 2015), contractile activity in the form of resistance exercise (RE) remains the most efficacious intervention. Mitochondrial dysfunction, changes in glycogen metabolism, and lipid accumulation are linked to insulin resistance in skeletal muscle. Athletes, laborers, and soldiers are well advised to consume diets containing a variety of foods rich in carbohydrates and other nutrients and to begin consuming such foods as soon as possible following glycogen-depleting exercise or activity.