Peptides > GHRH


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1. What Is Growth Hormone Releasing Hormone (GHRH)?


2. GHRH Structure


3. GHRH Is an Unusual Hormone


4. GHRH Research

What Is Growth Hormone Releasing Hormone (GHRH)?

Growth hormone releasing hormone (GHRH) is a naturally occurring peptide released by nerves, called arcuate neurons, in the hypothalamus. The peptide travels from the hypothalamus to the pituitary gland where it binds to the growth hormone releasing hormone receptor and causes the release of growth hormone (GH). It is critical for proper growth and development, increasing lean body mass and reducing adiposity (fat tissue). It is indirectly responsible for muscle growth and long bone growth, but has also been found to regulate inflammation, mitigate pain, and play an important role in the sleep-wake (diurnal cycle). It is released in a pulsatile manner from the hypothalamus and thus causes the pulsatile release of GH as well. This pattern of release is important to the function of growth hormone and thus to physiology in general.

GHRH Structure

Sequence: DL-Tyr-DL-Ala-DL-Asp-DL-Ala-DL-xiIle-DL-Phe-DL-xiThr-DL-Asn-DL-Ser-DL-Tyr-DL-Arg-DL-Lys-DL-Val-DL-Leu-Gly-DL-Gln-DL-Leu-DL-Ser-DL-Ala-DL-Arg-DL-Lys-DL-Leu-DL-Leu-DL-Gln-DL-Asp-DL-xiIle-DL-Met-DL-Ser-DL-Arg-DL-Gln-DL-Gln-Gly-DL-Glu-DL-Ser-DL-Asn-DL-Gln-DL-Glu-DL-Arg-Gly-DL-Ala-DL-Arg-DL-Ala-DL-Arg-DL-Leu
Molecular Formula: C215H358N72O66S
Molecular Weight: 5039.727 g/mol
PubChem CID: 44134750
CAS Number: 9034-39-3
Synonyms: Growth Hormone Releasing Factor, Somatocrinin, Somatoliberin

GHRH Is an Unusual Hormone

Growth hormone releasing hormone stands out among hormones due to its ability to exist in various forms. Its size can range from 37 to 44 amino acids, with the 44-amino-acid version being the most common and considered the standard reference when discussing GHRH. Interestingly, despite these differences in size, experimental evidence suggests that the overall function of the peptide remains unchanged. In other words, the 37-amino-acid version produces the same effects as its longer counterparts.

Growth hormone releasing hormone exhibits a basal rate of release that varies with age and developmental status, but its characteristic pattern of pulsatile release remains consistent regardless of the baseline hormone level. Research has indicated that maintaining the natural pulsation of GHRH, even during exogenous administration, is crucial for preserving normal physiological processes and preventing certain side effects.

What sets Growth hormone releasing hormone apart from other hormones is its exclusive presence within the hypothalamus in the central nervous system. While many hormones are widely distributed throughout the central nervous system, Growth hormone releasing hormone is not. However, It can also be found in peripheral tissues such as the pancreas, heart, thymus, and colon. It is worth noting that it has been detected pathologically in certain tumors.


GHRH Analogs Are Common

Several analogues of Growth hormone releasing hormone have been developed with the goal of selectively targeting specific effects of the peptide while avoiding others. Additionally, modifications have been made to extend the half-life of exogenously administered. Notable examples of GHRH analogues include:

  1. CJC-1295
  2. Sermorelin
  3. Tesamorelin

Of these, Tesamorelin stands out as it received FDA approval in 2010 for the treatment of lipodystrophy, a condition characterized by abnormal fat deposition, particularly in individuals with HIV. These analogues offer potential benefits while addressing specific medical conditions or therapeutic needs.

GHRH Research

Growth Hormone-Releasing Hormone, plays a significant role in sleep regulation, obesity, stress response, pain management, and several health conditions. Here’s a breakdown of its involvement in these areas:

1. Sleep Regulation: A substantial portion of the total GH released by the pituitary gland occurs during non-REM sleep (NREMS). Growth hormone releasing hormone has been found to promote NREMS, while suppressing normal it release inhibits NREMS. Studies in mice suggest that it is crucial in regulating the sleep cycle. Growth hormone releasing hormone levels can affect the balance between NREMS and REM sleep throughout the night. Obstructive sleep apnea (OSA) can lead to deficits in GH and Growth hormone releasing hormone levels, which may explain cognitive dysfunction and obesity in OSA patients. Correcting these deficits, possibly through Growth hormone releasing hormone supplementation, could help alleviate cognitive impairments associated with sleep apnea. There is also ongoing research into the link between GHRH and conditions like depression, which may be influenced by the balance between Growth hormone releasing hormone and corticotropin-releasing hormone (CRH).

2. Obesity: Growth hormone releasing hormone, by stimulating GH release, has anti-obesity properties. GH promotes lean body mass development, and GHRH supplementation has shown similar effects. Obesity reduces circulating GH levels by affecting GHRH secretion. This reduction in GHRH secretion may contribute to the difficulty of losing weight in obese individuals. It is speculated that GHRH or its analogs could be used to kickstart weight loss, helping to break the cycle of obesity.

3. Stress Response: Stress, whether physical or emotional, has been found to suppress Growth hormone releasing hormone secretion. This suppression can lead to delayed puberty, short stature, and depression. The mechanism involves neuropeptide Y levels, which alter the neurons responsible for Growth hormone releasing hormone production and release. This adaptation is thought to conserve energy during stressful events, but prolonged stress, particularly during childhood, can result in severe growth and development restrictions. GHRH supplementation may potentially offset the negative effects of severe physical and emotional distress on growth, development, inflammation, and cognition.

4. Pain Management: Research in rats has shown that GHRH is effective in relieving inflammatory pain without affecting the inflammatory mediators that cause it. This may have clinical relevance in fine-tuning the body’s inflammatory response to reduce pain without impacting other critical processes. GHRH could be particularly useful in managing the pain associated with fibromyalgia, a condition characterized by widespread pain, fatigue, and sleep disturbances. GHRH administration has been shown to reduce fibromyalgia pain and help reestablish normal sleep patterns.

5. Prostate Enlargement (BPH): Chronic inflammation is believed to play a role in benign prostatic hyperplasia (BPH or prostate enlargement). Research in mice suggests that GHRH antagonism can reduce inflammatory cytokines in the prostate, potentially leading to a reduction in prostate size. Furthermore, GHRH antagonism may prevent hyperplasia from developing in the first place, suggesting that GHRH antagonist therapy could be used as a preventive measure against BPH.

6. Muscle Growth in Aging: GH secretion and insulin-like growth factor-1 (IGF-1) decrease with age, resulting in reduced muscle mass and strength in older individuals. Research in older men has shown that multiple daily injections of GHRH or its analogs significantly improve muscle strength and bioenergetics without causing significant changes in other health parameters. GHRH supplementation also enhances sleep, potentially decreasing cardiovascular mortality, improving cognitive function, and boosting overall well-being. Long-term studies are underway to investigate the extended benefits and potential side effects of GHRH in countering the effects of aging.

These findings highlight the multifaceted role of GHRH in various physiological processes and potential applications in managing health conditions. Further research is needed to explore the full scope of its therapeutic potential.


Article Author

The above literature was researched, edited and organized by Dr. Logan, M.D. Dr. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.


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