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Regulation of Human Growth Hormone Secretion

HGH Secretion - Physiological Regulation of Growth Hormone Secretion

Human Growth Hormone is secreted in pulses.

The half-life of HGH is approximately 14 minutes. In between pulses, serum growth hormone is minimal or undetectable. Generally, growth hormone pulses occur approximately 10 times per day, lasting 90 minutes in length, and are separated by 128-minute intervals.[i]

Although it is typical in the US to suggest and require growth hormone to only be assessed in 24-hour sampling intervals for determining growth hormone deficiency and/or pituitary dysfunction, IGF-1 has been used successfully in various research for many years to assess HGH deficiency and optimization. The benefit of using IGF-1 is two-fold: 1) it is a safer and easier to test it with a blood test, and 2) IGF-1 is directly proportional to HGH production and is more stable, making it a good marker of measurement.

Human growth hormone decline is estimated to be around 50% every seven years in aging adults. This is dependent on a variety of factors. Many unique environmental influences related to one’s lifestyle can determine the quality of one’s human growth hormone secretion. Some of the more common factors are:

  • Nutritional factors
  • Sex Steroids
  • Ghrelin
  • GHRH
  • Sleep (GH normally reaches its peak within 1-hour of DEEP SLEEP.)

Promoters of Growth Hormone Secretion

Nutritional Factors – HGH Stimulators

  • Fasting can increase growth hormone secretion[i]
  • High protein meals[ii]
  • Intravenously administered amino acids[iii]

Sex Steroids – HGH Stimulators

Growth hormone is needed to control the tempo and progression of puberty in young boys. There is evidence of rising serum androgen concentrations and peak amplitude of human growth hormone in pubertal boys.[iv] Sex hormones can act centrally by regulating HGH secretion and peripherally by regulating HGH responsiveness. Sex hormones modulate HGH secretion directly and indirectly through IGF-1 modulation.[v]

GHRH – HGH Stimulators

The most well-known regulator is growth hormone releasing hormone GHRH. It is a 44 amino acid peptide hormone produced in the hypothalamus. The primary function of GHRH is to stimulate the release of human growth hormone in the body. GHRH is released from neurosecretory nerve terminals and is carried through the hypothalamos portal system to the anterior pituitary gland where it stimulates growth hormone secretion.  IGF-1 is a down-path hormone produced in the liver and other organs in response to growth hormone activity. IGF-1, along with HGH, work to cause metabolic and growth activities in the body.

Control of GHRH works similarly in the body to a thermostat system on an air-conditioner or furnace for temperature control. Stimulators marked in green in the chart stimulate, while inhibitors marked in “red” work to limit growth hormone secretion. As one side gets lower, the other side gets higher until balance or homeostasis occurs.

In many individuals, levels may not be optimal. This is potentially due to health status and age-related factors. Because of the obesity epidemic (70% overweight/obese) in the United States, growth hormone secretion is very often less than optimal. Other hormones such as testosterone and estrogens are influenced to a much greater degree by environmental and lifestyle factors than once believed. New evidence is showing hormone regulation is disrupted due to these factors. For one such example, see Testosterone Decline in Men – News <Click here>.


Regulation of Growth Hormone


Ghrelin is a gastrointestinal peptide hormone which acts as a nutritional positive regulator of human growth hormone. Ghrelin is secreted by the stomach and stimulates human growth hormone production. It has been observed that Ghrelin in obese children is reduced compared to leaner children, hence, this may be similar for adults as well.

Inhibitors of Growth Hormone Secretion


Somatostatin acts to inhibit human growth hormone release. It is released from the hypothalamus and it binds to five receptor sub-types.  Somatostatin is also known as a growth hormone inhibiting hormone (GHIH). Somatostatin also inhibits insulin and glucagon secretion. The release of somatostatin in the pituitary inhibits release of growth hormone, thyroid-stimulating hormone, and prolactin.  Somatostatin is also released in the gastrointestinal system to suppress the release of certain gastrointestinal hormones related to digestion and pancreatic hormones.


Insulin-like growth factor-1 mediates many of HGH’s peripheral actions and works to inhibit HGH secretion directly. IGF-1 is secreted in response to the activation of the growth hormone receptor by HGH secretion. IGF-1 is believed to be responsible for bone growth. It is also believed that growth hormone-independent of IGF-1 partially promotes bone growth as well since mice studies show IGF-1 at good levels along with very low levels of growth hormone had shorter bones. Both HGH and IGF-1 seem to have beneficial growth effects for bones, even as levels of IGF-1 are used to regulate growth hormone.

HGH stimulates IGF-1 secretion. It is estimated that approximately 75%-90% of IGF-1 production is done in the liver as HGH metabolizes. Fasting for one week has been shown to reduce IGF-1 by 50%. This seems counter-intuitive as fasting increases growth hormone secretion, yet still, IGF-1 is halved. Yet, under normal circumstances, an increase in growth hormone secretion generally increases IGF-1 when it metabolizes through the liver. It is believed this effect is due to a reduction of growth hormone sensitivity and growth hormone receptors under a fasting state.

When IGF-1 is injected into insulin resistant type-2 diabetes, insulin sensitivity improves. This is one indicator which may be linked to the positive benefits associated with improved body composition. Below are outcomes from those injecting exogenous growth hormone achieving higher IGF-1 levels taken from the Dr. Rudman HGH study shown below.


Growth Hormone Dr. Rudman Study


Glucocorticoids are a class of corticosteroids. These play a role in metabolism. Wikipedia: The name glucocorticoid (glucose + cortex + steroid) is composed of its role in the regulation of glucose metabolism, synthesis in the adrenal cortex, and its steroidal structure (see the structure to the right). They work as feedback in the immune system to reduce inflammation. Glucocorticoids up-regulates the expression of anti-inflammatory proteins and mutes proinflammatory proteins. Cortisol is the one important glucocorticoid as it regulates metabolic and homeostatic functions.

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[i] [Giustina A, Veldhuis JD. Pathophysiology of the neuro-regulation of growth hormone secretion in experimental animals and the human. Endocr Rev 1998; 19:717.]

[ii] [[Jaffe CA, DeMott-Friberg R, Barkan AL. Endogenous growth hormone (GH)-releasing hormone is required for GH responses to pharmacological stimuli. J Clin Invest 1996; 97:934.]

[iii] [Jaffe CA, DeMott-Friberg R, Barkan AL. Endogenous growth hormone (GH)-releasing hormone is required for GH responses to pharmacological stimuli. J Clin Invest 1996; 97:934.]

[iv] [Gh and Igf-1 Physiology in Childhood, Kavitha S Rozario, Catrin Lloyd, and Fiona Ryan.]

[v] [Pituitary Research Unit, Garvan Institute of Medical Research, Sydney, Australia. Meinhardt UJ, Ho KK 2006.]

[i] [Toogood AA, Nass RM, Pezzoli SS, et al. Preservation of growth hormone pulsatility despite pituitary pathology, surgery, and irradiation. J Clin Endocrinol Metab 1997; 82:2215.]