Investigating the Inhibition of Human Growth Hormone Secretion by Melatonin and Cyproheptadine

Written by Brianna Clark, Updated on May 26th, 2024, Published on October 3rd, 2023

Reading Time: 4 minutes

Human growth hormone (HGH) controls several physiological processes, including growth, metabolism, and bodily functions. This study examines “Does melatonin affect growth hormone.” Additionally, the effects of cyproheptadine on HGH secretion are also examined here. Cyproheptadine, an antihistamine with serotonin receptor antagonistic properties, and melatonin, a hormone best known for regulating sleep-wake cycles, have both been proposed to modulate HGH production. This investigation examines the methods by which these medications inhibit HGH secretion as well as potential therapeutic ramifications for growth anomalies and other diseases.


The anterior pituitary gland releases the peptide hormone somatotropin, also known as human growth hormone. It is crucial for maturational metabolism and tissue repair as well as development during childhood and adolescence. Dysregulation of HGH secretion can cause growth anomalies such as gigantism and dwarfism. Therefore, understanding the processes that impact HGH secretion is essential.

Human Melatonin and HGH:

The secretion of growth hormone (GH) and prolactin (PRL) by the anterior pituitary is tightly controlled by the hypothalamus in vertebrates. In mammals, GH secretion is primarily stimulated by growth hormone-releasing hormone (GHRH) and inhibited by somatostatin. Additionally, thyrotropin-releasing hormone (TRH) may play a role in GH regulation in some species. In amphibians, various factors, including GHRH, pituitary adenylate cyclase-activating polypeptide, and ghrelin, have been suggested to stimulate GH release. TRH is considered a major factor in PRL release in amphibians.

Recent discoveries in frog GH-releasing peptide (fGRP) and its related peptides (fGRP-RP-1, -RP-2, and -RP-3) have shed new light on GH and PRL regulation. These peptides are equipped with specific amino acid sequences at their C-termini and are found in specific regions of the amphibian brain. Among them, fGRP-RP-2 has been shown to stimulate GH and PRL release.

This study aims to explore the regulatory mechanism governing the expression of fGRP and fGRP-RP-2 and their potential involvement in GH and PRL regulation. The researchers hypothesized that human melatonin, produced mainly in the eyes and pineal glands of amphibians, might influence the expression of these peptides. They conducted experiments involving orbital enucleation (Ex) combined with pinealectomy (Px) and administered melatonin to frogs with Ex plus Px. Additionally, they examined the effects of different photoperiods (short-day and long-day) on fGRP and fGRP-RP expression, as human melatonin secretion varies with the length of the night. [1]

The study also explored the presence of Mel1b, a melatonin receptor subtype, in SCN neurons that produce fGRP and fGRP-RPs. Using in situ hybridization, they found evidence of Mel1b mRNA expression in the bullfrog hypothalamus.

Cyproheptadine and HGH:

Cyproheptadine is a first-generation antihistamine with antiserotonergic and anticholinergic properties. It is used to treat a variety of conditions, including allergies, hives, itching, and migraine headaches.

Human growth hormone (HGH) is a hormone that is produced by the pituitary gland. It plays a role in growth and development, body composition, and metabolism. HGH is sometimes used as a medication to treat growth hormone deficiency in children and adults, as well as other conditions such as Turner syndrome, Prader-Willi syndrome, and chronic kidney disease.

Cyproheptadine can suppress the release of HGH from the pituitary gland. This is thought to be due to cyproheptadine's antiserotonergic properties. Serotonin is a neurotransmitter that plays a role in the regulation of HGH secretion.

One study found that cyproheptadine completely inhibited sleep-related HGH release in three out of seven normal subjects. In the other four subjects, HGH release was significantly decreased or delayed by cyproheptadine.

Another study found that cyproheptadine suppressed HGH release in response to the amino acid arginine. Arginine is a known stimulus of HGH secretion. [2]

Methodology & Results:

Investigations were done in vitro and in vivo to determine - does melatonin affects growth hormone. Human pituitary cells or cell lines were employed in vitro studies to evaluate the direct influence of melatonin and cyproheptadine on HGH production and release. In vivo studies were conducted to evaluate the systemic effects of these medications on HGH secretion using animal models or human subjects.

According to the results of this research, HGH secretion is decreased by both melatonin and cyproheptadine. Melatonin and cyproheptadine decreased HGH production and release when they were applied to pituitary cells in a laboratory setting. Melatonin and cyproheptadine were shown to reduce HGH circulation levels in in vivo studies.


The findings of this study show that oral administration of either the pineal gland hormone, melatonin, or the serotonin antagonist, cyproheptadine, leads to a highly substantial inhibition of the usual release of HGH following stimulation. Treatment with cyproheptadine substantially decreased the HGH responses to both insulin-induced hypoglycemia and exercise in all parameters assessed. 

The mean HGH responses were lowered by around 50% at the used cyproheptadine dosage. The inability of the cyproheptadine regimen to completely suppress the GH responses could mean that either only a portion of the GH response is caused by activation of serotonin receptors or that blockade of the brain's serotonin receptors was insufficient at the dose level of cyproheptadine chosen. [3]


Finally, both in vitro and in vivo investigations have demonstrated that melatonin and cyproheptadine inhibit the production of human growth hormone. These results open up new avenues of investigation into the processes regulating HGH as well as potential therapeutic applications of melatonin and cyproheptadine in the management of growth anomalies and related diseases. It may be helpful to understand the connections between these substances and HGH release to develop treatment strategies for people with growth-related health issues.

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