Testosterone Signaling Integrity describes the optimal functional status of the entire biological pathway by which the testosterone molecule exerts its effects on target cells and tissues. This integrity encompasses the hormone’s free circulation, its successful binding to the androgen receptor, and the subsequent activation of intracellular genomic and non-genomic cascades. Compromised integrity, often due to receptor downregulation or increased Sex Hormone Binding Globulin (SHBG), can lead to symptoms of deficiency even with normal total testosterone levels. Maintaining this integrity is crucial for muscle mass, bone density, and neurological health.
Origin
This term originates from molecular endocrinology, emphasizing that the simple measurement of hormone concentration is insufficient; the biological effect must be considered. The concept evolved from the understanding of receptor pharmacology and the role of cofactors and binding proteins in modulating hormone action. It highlights the distinction between hormone levels and hormone action.
Mechanism
The mechanism begins with free testosterone entering the cell and either binding to the cytosolic androgen receptor (AR) or being converted to dihydrotestosterone (DHT). The activated AR-hormone complex then translocates to the nucleus to bind to specific DNA sequences, modulating gene expression for anabolic effects. Integrity relies on the correct concentration of free hormone and the functional status of the AR, which can be influenced by metabolic health and nutrient status.
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