In the hypothalamus, a kind of nerve cell called an arcuate neuron secretes a growth hormone-releasing hormone (GHRH) peptide. Studies suggest the peptide is released from the hypothalamus and may reach the pituitary gland, activating the growth hormone-releasing hormone receptor. Research suggests that GHRH may be indirectly responsible for the development of muscles and long bones. It may also control inflammation, reduce pain, and play a major part in the sleep-wake (diurnal) cycle. It has been theorized to trigger periodic GH secretion because of its pulsatile hypothalamic release. The growth hormone’s physiologic role is dependent on this release rhythm.
GHRH and Other Hormones
Unlike most other hormones, GHRH comes in a variety of forms. Its size may vary from 37 to 44 amino acids, with the 44-amino-acid variant being the most prevalent and the conventional reference when discussing GHRH. Interestingly, experimental data suggests that the peptide’s overall function is unaffected by its size; thus, the 37-amino-acid long variant may have the same effects as the longer version.
The resting rate of GHRH release changes over time and stage of development, but the pulsatile release pattern is constant. As suggested by studies, maintaining the natural pulse of GHRH may be crucial for maintaining normal physiology and avoiding certain negative effects.
In contrast to other hormones, GHRH is only produced in the hypothalamus of the central nervous system. While many hormones are broadly disseminated throughout the CNS, GH appears not to. However, GHRH is suggested to be present in other organs and tissues, such as the heart, thymus, pancreas, and colon. It has also been theorized to be detected pathologically in some cancers.
The pituitary gland secretes most of its growth hormone (GH) during non-rapid eye movement sleep (NREMS). Findings imply that natural GHRH release suppression may reduce NREMS, whereas GHRH presentation may increase NREMS. Research in mice suggests that GHRH may play a crucial role in controlling the circadian rhythm of sleep. Intriguingly, the equilibrium between GH and GHRH secretion may explain why animals alternate between non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REM) every few hours. Research on mice purports that elevating GHRH levels may increase GH and NREMS secretion. As GH levels rise, REM sleep duration has been speculated to extend, and GHRH secretion may decrease. Naturally, this is proposed to increase GHRH secretion and kick off the cycle once again. Alterations to sleep schedule may have far-reaching effects, and it’s possible that a lot of sleep disorders may be traced back to issues with this axis.
Obstructive sleep apnea (OSA) is well-known to induce a range of neuroendocrine dysfunctions and may lead to anything from heart disease to cognitive dysfunction. The substantial impairments in GH and GHRH levels seen in research models of OSA may help to explain the proposed link between OSA and cognitive impairment and obesity. Research models of OSA given GHRH may have a more rapid recovery and fewer long-term complications, as suggested by some research.
GHRH levels are theorized to be normal in research models with OSA with no cognitive problems. As a result, GHRH has been the focus of research into a variety of neurological disorders, including Alzheimer’s.
Corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone (GHRH) levels may be discordant. This disproportion has been linked to a loss of short-wave sleep and a release of REM sleep inhibition. Although these studies are still in their infancy, there is reason to speculate that a better grasp of the GHRH-CRH balancing act may support physiological function.
Significant sleep and mood disorders are common after traumatic brain injury (TBI) because of damage to the GHRH-GH axis. In 2017, researchers conducted a phase 2 clinical experiment to see how the GHRH analog Tesamorelin may affect sleep in research models of TBI. The experiment aimed to see whether the peptide, instead of a placebo, might alter the time spent in NREM sleep. Although the study’s findings have not yet been published, they suggest a significant interest in GHRH and its potential to control sleep patterns.
Investigations purport that GHRH may act as a possible muscle-building and weight-reducing peptide by increasing GH production. It has been speculated that GHRH may mimic GH’s effects in encouraging lean body mass growth. Studies have purported that obesity reduces GH levels in the blood by interfering with GHRH secretion. Obesity has been linked to reduced GHRH secretion, suggesting that this phenomenon may partially explain this abnormality. The more fat the organism stores, the less GHRH is secreted. Until the cycle is interrupted and endocrine balance is restored, scientists propose that GHRH (or a GHRH analog) may induce fat cell dissipation and dissolution.
GHRH and Stress Hormones
Both physical and psychological stress may lead to a suppression of GHRH secretion. Rigorous studies have purported that stress, especially psychological stress, may contribute to delayed development and changes in dimension. Although the relationship between stress and GHRH levels has been proposed, the specific mechanism by which stress affects GHRH was unknown until recent studies have posited speculative claims.
Recent studies have hinted that alterations in neuronal activity that produce and secrete GHRH may be responsible for the speculated variations in GHRH secretion. The reduced GHRH secretion is assumed to be a survival mechanism used during starvation to save energy. This mechanism may be triggered by a concentrated wave of stress hormone release, and chronic stress may severely limit growth.
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References
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[iii] F. Obal, J. Alt, P. Taishi, J. Gardi, and J. M. Krueger, “Sleep in mice with nonfunctional growth hormone-releasing hormone receptors,” Am. J. Physiol. Regul. Integr. Comp. Physiol., vol. 284, no. 1, pp. R131-139, Jan. 2003
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