Steroidogenic enzyme content and T concentrations in skeletal muscle are similar between men and women (17). The magnitude of the acute responses is affected by many factors including the demands of the protocol, nutritional intake, training experience but mostly due to plasma volume reductions and reduced clearance (1). Nevertheless, SHBG concentrations influence T binding capacity and FT available for diffusion across the cell membrane. Khajehnasiri et al. (13) examined moderate vs. intense treadmill training for 6 months in rats and showed intense exercise (but not moderate) led to decreased GnRH mRNA and serum total T (TT) and LH. Hypothalamic neuropeptide expression is dependent on metabolic status (12); however, little is known regarding exercise responses. Human and animal studies (using a variety of research models) demonstrated the importance of androgens for maintaining and increasing skeletal muscle strength and mass. Positive correlations were shown between AR protein content and Wnt5 expression and muscle mass and Wnt5 expression in rats (44). Genomic androgen/AR binding may enhance muscle performance via stimulating the Wnt-β-catenin pathway. Testosterone may be anti-catabolic by either decreasing glucocorticoid receptor (GR) expression, interfering with cortisol binding, or the AR-T complex may compete with cortisol-GR complex for Cis-element binding sites on DNA (and vice versa). Glucocorticoids also may blunt skeletal muscle protein synthesis by inhibiting IGF-I signaling, a muscle anabolic growth factor, and increasing myostatin signaling, a muscle catabolic growth factor, contributing to muscle atrophy (207, 209, 210). To the contrary, anabolic resistance and sarcopenia may be attributed to dysregulation in the IGF stimulated, Akt /Protein Kinase B and mechanistic target of rapamycin (mTOR) signaling pathways in response to resistance exercise and protein intake (164). Several studies have shown systemic elevations in IGF-I produced no elevations in protein synthesis or hypertrophy during resistance exercise training whereas up-regulation in the muscle isoform was linked to significant muscle hypertrophy (151). Taken together, these results indicated for the first time that acute and chronic exercise training using conventional large muscle group resistance training protocols will increase (acutely and chronically) plasma concentrations of GH bioactivity in young women. The FT-AR complex inhibits GSK-3 and increases β-catenin where it translocates to the nucleus, binds to DNA response elements (T-cell factor/lymphoid enhancer factor 1 –TCF/LEF), increases transcription, and activation of muscle satellite cells. Indeed estrogen replacement has been shown to attenuate the age-related decline in muscle mass observed in postmenopausal women (Enns and Tiidus, 2010). Anabolic effects of AR and testosterone upregulation after RE occur through a combination of both genomic i.e., transcriptional capacity, and non-genomic i.e., translational efficiency, pathways (Kraemer et al., 2020). This reduction can eventually lead to very low resting concentrations of circulating testosterone particularly in men, creating the so-called andropause (Vingren et al., 2010). Because testosterone is bound to SHBG with high affinity, it is not available to most tissues for action. With aging, there is a linear decline in bioavailable circulating testosterone in both men and women (Kraemer et al., 1998; Hakkinen et al., 2000), with these reductions leading to osteoporosis in both sexes (Mohamad et al., 2016).
