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Although the mechanisms remain uncertain, it is hypothesized that the term HPA axis is more susceptible to glucocorticoid-mediated downregulation of central GR expression, leading to impaired negative feedback regulation

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In contrast to the specific effects of GHRT by peptides directly within the GH neuroendocrine axis, GHS enhances secretory performance because it mitigates the progressive, maladaptive dominance of intrinsic factors such as sermorelin/GHRH and somatostatin (Figure 4)