Testosterone is the primary male sex hormone that plays a vital role in the development and maintenance of male characteristics. Testosterone binds to and activates androgen receptors (AR) and elicits its effects on the body.
There is evidence that testosterone can increase androgen receptor levels under certain conditions:
- Multiple studies have shown that giving supraphysiological doses of testosterone to men leads to an upregulation or increase in androgen receptor levels in skeletal muscle. This may enable testosterone to exert more of its muscle-building effects.
- Castration of male rodents leads to a downregulation or decrease in AR levels. Administering testosterone post-castration can bring AR density back to baseline or slightly elevated levels. This indicates testosterone helps maintain physiological AR levels.
- Testosterone administration in orchidectomized male primates has been shown to significantly increase AR mRNA and binding capacity levels in the striated perineal muscle.
- There is some research showing that long-term testosterone administration to hypogonadal men increased AR levels in fat cells and quadriceps muscle compared to baseline.
However, the effects of testosterone on AR levels depend on several factors:
- Type of tissue: Testosterone seems to upregulate ARs more robustly in skeletal muscle and bone tissue rather than prostate tissue. The effects can vary based ontissue-specific co-activators of AR signaling.
- Timing and duration of dosing: Acute vs chronic testosterone dosing can have different effects. For example, a single high dose may decrease AR levels temporarily before they rebound.
- Presence of other hormones and growth factors: Estrogen, IGF-1, growth hormone can alter how testosterone regulates AR content.
- Subject characteristics: Effects likely differ between healthy men, hypogonadal men, those with chronic diseases, and animal models.
The mechanism behind testosterone increasing androgen receptors may involve:
- Testosterone directly enhancing AR gene expression and stability of AR messenger RNA.
- Post-transcription effects enhancing AR protein synthesis.
- Slowing rate of AR breakdown by inhibiting proteases.
- Sensitizing cells to the effects testosterone by upregulating co-activators.
In most cases, more androgen receptors allow tissues and cells to become more sensitive and responsive to the actions of testosterone and DHT. This enhancement of androgenic signaling can amplify the anabolic effects in muscle and bone.
However, there is likely an upper limit beyond which further boosting AR content no longer augments testosterone effects. Excessively high AR density could potentially promote androgen-sensitive pathology in the long run.
The interaction between testosterone and androgen receptors is complex with many influencing variables. While testosterone can increase AR levels under certain conditions, this upregulation is controlled by multiple checks and balances in the body. Maintaining testosterone levels in the healthy physiological range is important for optimal androgen signaling and male health.