Growth Hormone-Releasing Hormone (GHRH) is a peptide hormone produced by nerve cells in the hypothalamus, a small region at the base of the brain. Its primary role is to prompt the anterior pituitary gland to synthesize and secrete Growth Hormone (GH). This process begins in the fetal stage, with GHRH first appearing in the human hypothalamus between 18 and 29 weeks of gestation. Once released, GH acts on the body’s tissues to regulate growth and metabolism, while GHRH also influences sleep and food intake.
How GHRH Functions in the Body
GHRH is secreted by hypothalamic neurons and travels through the hypophyseal portal system, a dedicated network of blood vessels connecting the hypothalamus to the anterior pituitary gland. This route delivers the hormone efficiently and in high concentration without it being diluted in the general bloodstream.
Upon arrival at the anterior pituitary, GHRH binds to its specific receptor on pituitary cells known as somatotrophs. This binding triggers a cascade of signals within the cell, activating enzymes that increase the concentration of a signaling molecule called cyclic AMP (cAMP).
This surge in cAMP ultimately leads to the transcription of the GH gene. This process switches on the cellular machinery responsible for producing new GH molecules, which are then packaged and released into the bloodstream.
Control of GHRH Release
The secretion of GHRH is managed by feedback loops and external signals. When GHRH stimulates the pituitary to release Growth Hormone (GH), the resulting increase in blood GH levels signals the hypothalamus to reduce GHRH production. GH also stimulates the liver to produce Insulin-like Growth Factor 1 (IGF-1), which is another potent inhibitor of GHRH release.
Another hormone from the hypothalamus, somatostatin, acts as the primary antagonist to GHRH by directly inhibiting the pituitary’s release of GH.
Physiological states also influence GHRH secretion. Deep sleep, physical exercise, and low blood glucose levels are known to stimulate its release, which helps explain the pulsatile nature of GH secretion. Conversely, high blood glucose can suppress GHRH release. The hormone ghrelin, produced in the stomach in response to hunger, also stimulates GHRH secretion.
Impact of GHRH Levels on Health
Disruptions in GHRH production can have significant health consequences. A GHRH deficiency leads to insufficient Growth Hormone (GH) secretion, a condition known as GH deficiency. In children, this results in slowed growth rates and shorter stature.
In adults, GHRH deficiency and the subsequent lack of GH can cause a range of symptoms, including:
- Reduced muscle mass and strength
- An increase in body fat, particularly around the abdomen
- Decreased bone density, elevating the risk of fractures
- Reduced energy levels and an impaired quality of life
Conversely, an overproduction of GHRH, though rare, leads to excessive GH secretion, usually caused by a tumor. If this excess occurs in childhood before bone growth plates have fused, it results in gigantism. In adulthood, GHRH excess causes acromegaly, a condition marked by the enlargement of bones in the hands, feet, and face, along with other complications.
GHRH in Medicine
GHRH and its synthetic versions are used for both diagnostic and therapeutic purposes. A primary diagnostic tool is the GHRH stimulation test, which involves administering GHRH and measuring the pituitary’s subsequent release of Growth Hormone (GH). This test helps determine if a GH deficiency originates in the hypothalamus (insufficient GHRH) or the pituitary (inability to respond).
Synthetic forms of GHRH, known as GHRH analogs, are used therapeutically. The analog sermorelin treats certain cases of GH deficiency by stimulating the patient’s pituitary to produce its own GH, offering an alternative to direct GH injections.
Another analog, tesamorelin, is approved for reducing excess abdominal fat in patients with HIV-associated lipodystrophy, a condition involving abnormal fat distribution.