Growth Hormone, Testosterone, Peptides, and Circadian Biophysics: A Comprehensive Perspective

The hormonal landscape, growth hormone (GH), testosterone, estrogen, and their interplay, is intricately regulated by coupled feedback loops. When disrupted, these systems can promote cancer growth under specific conditions. While peptides offer one way to modulate these hormones, they represent an exogenous intervention that risks overriding the body's natural signaling. Instead, leveraging light, food timing, and circadian biophysics provides a sustainable, endogenous approach to hormone optimization.

The Role of Peptides and Natural Regulation

Peptides that stimulate GH or testosterone can offer benefits but also carry risks of bypassing the body's innate hormonal checks and balances. These interventions may inadvertently amplify hormonal cascades in ways that promote cancer, particularly in individuals with heightened aromatase activity or high estrogen levels.

• Endogenous Peptide Production: Light and food timing act as natural regulators, enhancing the body's ability to produce peptides like GHRH (growth hormone-releasing hormone) and others. Proper circadian alignment ensures these signals remain in balance, reducing the risks associated with exogenous manipulation.
  
  

Evolutionary Basis of Hormonal Light Regulation – The human hormonal system evolved under consistent environmental light-dark cues. Before artificial lighting, sunrise and sunset provided dependable time cues (zeitgebers) for hormonal release. Disruption of these cues in modern life leads to desynchronization between central (SCN-mediated) and peripheral clocks (in liver, gonads, skin), resulting in hormonal resistance syndromes, impaired testosterone pulsatility, and reduced growth hormone amplitude. Re-entraining these rhythms through natural light exposure restores synchrony across systems, reversing symptoms often mistaken for age-related decline.

Ray Peat's Work: Strengths and Limitations

Ray Peat’s protocols focus heavily on metabolism and energy production, emphasizing the role of thyroid function, progesterone, and avoiding excessive estrogen dominance. His dietary recommendations (e.g., sugar, dairy, and saturated fats) are designed to enhance mitochondrial function and lower stress hormones.

• Strengths: These principles can support hormone balance by improving metabolic flexibility and reducing oxidative stress.

• Limitations: Peat’s work lacks a strong emphasis on circadian biophysics, the critical role of light, darkness, and timing in regulating hormonal cascades. For example:

• Circadian light exposure directly influences leptin, melatonin, and GH signaling.

• Endogenous production of key hormones and peptides relies on the synchronization of these signals, which is often overlooked in metabolism-centered protocols.
  
  

The Photonic Hormonal Loop: A Deeper Biophysical Mechanism – Beyond circadian timing, light at specific wavelengths triggers photoreceptors such as neuropsin (OPN5) and melanopsin (OPN4) in the skin, gut, retina, and brain. These photoreceptors regulate hormones like GnRH, FSH, LH, leptin, and prolactin, influencing testosterone, estrogen, and GH indirectly. This photonic control system forms a recursive loop: light activates hormones that affect behavior (e.g., food seeking, sleep drive), which then realigns the system's sensitivity to light the next day. Disrupting this loop through night-time artificial light leads to hormonal rigidity and metabolic chaos.

Circadian Biophysics and Hormonal Feedback Loops

1. Light and Darkness as Primary Signals:

• GH’s largest release occurs during sleep (11 PM–4 AM), initiated by a cascade of leptin (from 4h of darkness on the eyes skin and digestive tract – remember eating food is eating light), melatonin (after 4 hours of darkness), and prolactin. This orchestrates autophagy, clearing precancerous cells and preventing tumor growth or metastasis. This is the important cascade to get right to lower any risks of any subsequent peptide or GH simulating therapies.

• Interruptions (e.g., artificial light, nighttime waking) break this cascade, impairing autophagy and leaving damaged cells unchecked withi increased aromatase activity hence high testosterone fuelling high estrogen and blunting endogenously produced growth hormone release.

• Prolactin’s Critical Role Post-Darkness – Prolactin, often overlooked, is released 4–6 hours after melatonin onset and is essential for the GH surge during sleep. It supports neurogenesis, tissue regeneration, and immune modulation. Any light exposure after sunset, especially from screens or indoor lighting, blunts prolactin release, disrupting the GH-autophagy axis. Thus, protecting post-sunset darkness in the eyes and skin is as critical as sunrise exposure for hormonal optimization.

2. Hormonal Cascades and Cancer Risks:

• Elevated GH in a high-estrogen environment drives cellular proliferation, increasing cancer risks, particularly in hormone-sensitive tissues. Add low grade chronic inflammation to this mix and you have a problem no peptide or supplement can benefit. Fix the circadian cascade of hormones first and you’ll lower risks of any complications.

• High testosterone, when paired with enhanced aromatase activity, leads to higher estradiol and SHBG levels, exacerbating estrogen’s effects. This highlights the importance of balancing testosterone and mitigating aromatase via circadian regulation, light exposure, and inflammation control. So raising T and GH as a goal is not wise because it’s a half truth and fails to consider all the interconnected hormone interactions and if done without addressing leptin or melatonin for example, can lead to a pro-growth state for not just muscle tissue.

• Estrogen Dominance, Aromatase, and Mitochondrial Light Signaling
  Aromatase, the enzyme that converts testosterone to estradiol, is upregulated by blue light, inflammation, and EMF exposure, all common in indoor lifestyles. Red and near-infrared light have been shown to downregulate aromatase activity and restore androgen balance. Supporting mitochondrial redox tone via light enhances energy production and shifts hormonal ratios in favor of anabolism without exogenous testosterone. Estrogen dominance is often not a hormone issue, but a circadian redox signaling dysfunction.

3. Food Timing and Hormonal Synchronization:

• Meal timing directly affects leptin and insulin, which regulate downstream hormones like GH and testosterone. Properly timed meals align metabolic and hormonal rhythms, enhancing the body’s endogenous production of peptides and reducing reliance on exogenous interventions. Food is a daylight signal to the gut.

The Biophysical Approach: A Better Way Forward

Rather than “playing doctor” with peptides or hormonal therapies, focusing on circadian biophysics ensures natural regulation of hormonal pathways:

• Light Exposure: Early AM full-spectrum light on the eyes and skin and a protein rich breakfast, with light exposure particularly at infrared and ultraviolet wavelengths like 1280 nm (near-infrared) and 380 nm (UV), is essential for regulating mitochondrial ROS, mTOR, optimizes cortisol, insulin, ghrelin, testosterone and dopamine; evening darkness in the eyes, skin and gut, sensitizes leptin and boosts melatonin, and sets the stage for GH and autophagy.

• Food Timing: Eating earlier aligns leptin and insulin with circadian rhythms, supporting GH pulsatility during sleep. Stacking intermittent fasting in the AM rather than the PM is a big win metabolically.

• Sleep Optimization: Prioritizing consistent sleep schedules, artificial visible and non-visible light exposure mitigation and prolactin-dopamine cycle signals post sunset ensures the leptin-melatonin-prolactin-GH feedback loop operates efficiently. Leaving you with less adipose fat and more lean muscle mass upon waking.
  
  

Some peptides, foods/nutrients that can help GH

• Ipamorelin: A GHRP that selectively stimulates GH release with minimal side effects. This will make you hungry as it simulates ghrelin too, remember don’t give in to the hunger before bed, food is light in the belly and you don’t’ want this after sunset.

• Tongkat Ali: A herbal supplement that boosts testosterone and improves male reproductive health.

• Vitamin A from Seafood: Supports testosterone synthesis and hormonal balance.

• Iodine and Thyroid Support from Seafood: Enhances thyroid function, crucial for testosterone regulation.

• Kisspeptin: Stimulates GnRH release, promoting testosterone production (requires careful monitoring).

• CJC-1295: A GHRH analog that encourages GH secretion and indirectly supports testosterone levels (requires careful monitoring).
  
  

Takeaway

Ray Peat’s insights into metabolism are valuable but incomplete without the foundation of circadian biophysics. By integrating light, darkness, and timing, we harness the body’s natural ability to produce peptides and regulate hormones. This endogenous approach optimizes health while minimizing risks, such as cancer promotion from imbalanced hormonal cascades. Endogenous control is not only safer but also aligns with the body’s evolutionary design to maintain harmony. Once you have this as a foundation you can add peptides or supplements if you so choose as they will have more of a safe user profile and be able to give you the boost you may be looking for.

References

Leptin, growth hormone, and prolactin also exhibit circadian secretion patterns, with light exposure and SCN signaling modulating their rhythmicity.

• Direct Effects of the Light Environment on Daily Neuroendocrine Control. Paul S, Brown T. The Journal of Endocrinology. 2019;:JOE-19-0302.R1. doi:10.1530/JOE-19-0302.

• Circadian Mechanisms in Medicine. Allada R, Bass J. The New England Journal of Medicine. 2021;384(6):550-561. doi:10.1056/NEJMra1802337.

Extraocular photoreceptors, such as neuropsin in the skin, may play a role in peripheral circadian regulation

• Molecular Pathways Regulating Circadian Rhythm and Associated Diseases. Ding M, Zhou H, Li YM, Zheng YW. Frontiers in Bioscience (Landmark Edition). 2024;29(6):206. doi:10.31083/j.fbl2906206.

PBM at 808 nm increased cerebrovascular testosterone concentrations, with effects mediated in part by 17β-hydroxysteroid dehydrogenase 5 (17β-HSD5), but not aromatase. The same study found that androgen receptor antagonism reversed the beneficial effects of PBM, indicating a role for testosterone signaling in the observed neurovascular protection.

• Activation of Testosterone-Androgen Receptor Mediates Cerebrovascular Protection by Photobiomodulation Treatment in Photothrombosis-Induced Stroke Rats. Feng Y, Huang Z, Ma X, et al. CNS Neuroscience & Therapeutics. 2024;30(2):e14574. doi:10.1111/cns.14574.

Prolactin and growth hormone both exhibit nocturnal peaks under normal conditions; circadian misalignment (e.g., shift work, light at night) blunts or shifts these peaks, potentially altering cell proliferation and immune surveillance, which are implicated in hormone-dependent cancers such as breast cancer. Leptin and insulin rhythms are similarly disrupted, leading to metabolic dysregulation, increased adiposity, insulin resistance, and chronic low-grade inflammation—all of which are established cancer risk factors. Estrogen signaling is also affected, as circadian disruption can alter the expression of enzymes involved in estrogen synthesis and metabolism, contributing to increased risk for hormone-dependent malignancies.

• The Pathophysiologic Role of Disrupted Circadian and Neuroendocrine Rhythms in Breast Carcinogenesis. Ball LJ, Palesh O, Kriegsfeld LJ. Endocrine Reviews. 2016;37(5):450-466. doi:10.1210/er.2015-1133.

• "Time" for Obesity-Related Cancer: The Role of the Circadian Rhythm in Cancer Pathogenesis and Treatment. Miro C, Docimo A, Barrea L, et al. Seminars in Cancer Biology. 2023;91:99-109. doi:10.1016/j.semcancer.2023.03.003.

• The Impact of Sleep and Circadian Disturbance on Hormones and Metabolism. Kim TW, Jeong JH, Hong SC. International Journal of Endocrinology. 2015;2015:591729. doi:10.1155/2015/591729.

• The Relationship Between Circadian Rhythm and Cancer Disease. Munteanu C, Turti S, Achim L, et al. International Journal of Molecular Sciences. 2024;25(11):5846. doi:10.3390/ijms25115846.

Epidemiologic data consistently link circadian disruption (especially night shift work and light at night) to increased incidence of breast, prostate, colorectal, and other cancers, supporting the biological plausibility of these hormonal mechanisms.

• Circadian Disruption in Cancer Hallmarks: Novel Insight Into the Molecular Mechanisms of Tumorigenesis and Cancer Treatment. Zhou Z, Zhang R, Zhang Y, et al. Cancer Letters. 2024;604:217273. doi:10.1016/j.canlet.2024.217273.

• Cancer in the Fourth Dimension: What Is the Impact of Circadian Disruption?. Pariollaud M, Lamia KA. Cancer Discovery. 2020;10(10):1455-1464. doi:10.1158/2159-8290.CD-20-0413.