Me: It seems the hypothalamic-pituitary pathway system not only releases growth hormones (GH) but also growth hormone secretagogues (GHS). The human body releases growth hormones throughout life, which decreases to a lower rate later in life. At the same time the growth hormone is being released, the growth hormone inhibiting somatostatin is also released at the same time. It would appear that as time moves forward and we grow older, the rate of somatostatin release increase, until it overtakes the rate of GH release. remember that the release of GH by the pituitary is controlled by growth hormone releasing hormone and somatostatin in the hypothalamus.
The synthetic type of GH we could take after reaching physical maturity would have to be in injection form. However, this method is not in the pulsating fashion that GH is supposed to act in the body. Naturally, the hypothalamic-pituitary system releases GH in a pulsation way into the body. The secretagogues are peptides made of 6 amino acids linked together. These GHS can be taken orally without the stomach digesting the peptide and breaking it up effectively destroying it.
It seems that GHS like MK-677 in experiments have mixed results. The link says that the authors think GHS works because it mimics ghrelin towards the body’s GH receptors. If I was asked whether GHS can be used to increase height, I would say it could work for people who are of short stature due to low growth hormones in the system but probably little else. THe IGF-1 level was shown to increase from GHS intake from the first study below.
From the website Iron Man Magazine, a well written article on GHS.
From the website on The Journal Of Endocrinology & Metabolism
Effects of an Oral Growth Hormone Secretagogue in Older Adults
- Heidi K. White, Charles D. Petrie, William Landschulz, David MacLean, Ann Taylor,Kenneth Lyles, Jeanne Y. Wei, Andrew R. Hoffman, Roberto Salvatori, Mark P. Ettinger,Miriam C. Morey, Marc R. Blackman, George R. Merriam and for the Capromorelin Study Group
Duke University School of Medicine and Geriatric Research Education and Clinical Center (GRECC), Durham Veterans Affairs (VA) Medical Center (H.K.W., K.L., M.C.M.), Durham, North Carolina 27710; Pfizer Global Research and Development (C.D.P.), Groton, Connecticut 06340; Endocrine Clinical Research (W.L.), Eli Lilly and Co., Indianapolis, Indiana 46285; Brown University Medical School (D.M.), Providence, Rhode Island 02912; Novartis (A.T.), Cambridge, Massachusetts 02139; GRECC, Central Arkansas Veterans Affairs (VA) Healthcare System, and University of Arkansas for Medical Sciences (J.Y.W.), Little Rock, Arkansas 72205; VA Palo Alto Health Care System and Stanford University (A.R.H.), Palo Alto, California 94304; The Johns Hopkins University School of Medicine (R.S.), Baltimore, Maryland 21205; Radiant Research and the Regional Osteoporosis Center (M.P.E.), Stuart, Florida 34996; Washington DC VA Medical Center (M.R.B.), Washington, D.C. 20422; and VA Puget Sound Health Care System and University of Washington School of Medicine (G.R.M.), Seattle and Tacoma, Washington 98493
- Address all correspondence and requests for reprints to: Heidi K. White, M.D., M.H.S., Duke University School of Medicine, Box 3003, Durham, North Carolina 27710. E-mail:White031@mc.duke.edu.
Context: GH secretion declines with age, possibly contributing to reduced muscle mass, strength, and function. GH secretagogues (GHS) may increase muscle mass and physical performance.
Objectives/Design: We conducted a randomized, double-masked, placebo-controlled, multicenter study to investigate the hormonal, body composition, and physical performance effects and the safety of the orally active GHS capromorelin in older adults with mild functional limitation.
Intervention/Participants: A total of 395 men and women aged 65–84 yr were randomized for an intended 2 yr of treatment to four dosing groups (10 mg three times/week, 3 mg twice a day, 10 mg each night, and 10 mg twice a day) or placebo. Although the study was terminated early according to predetermined treatment effect criteria, 315 subjects completed 6 months of treatment, and 284 completed 12 months.
Results: A sustained dose-related rise in IGF-I concentrations occurred in all active treatment groups. Each capromorelin dose prompted a rise in peak nocturnal GH, which was greatest with the least frequent dosing. At 6 months, body weight increased 1.4 kg in subjects receiving capromorelin and decreased 0.2 kg in those receiving placebo (P = 0.006). Lean body mass increased 1.4 vs. 0.3 kg (P = 0.001), and tandem walk improved by 0.9 sec (P = 0.02) in the pooled treatment vs. placebo groups. By 12 months, stair climb also improved (P = 0.04). Adverse events included fatigue, insomnia, and small increases in fasting glucose, glycosylated hemoglobin, and indices of insulin resistance.
Conclusions: In healthy older adults at risk for functional decline, administration of the oral GHS capromorelin may improve body composition and physical function.
From the Dr. Lam website article on Growth Hormones And Growth Hormone Secretagogues located HERE…
B. Amino Acid Secretagogues
A secretagogue (pronounced se-cre’-ta-gog) is a natural polyamino acid chain that is postulated to initiate the pituitary gland to release growth hormone. It is the precursor to hGH. While hGH causes the body to act as if the pituitary has released growth hormone, a secretagogue actually causes the release of it. Hence a secretagogue causes the bodies own natural processes to produce growth hormones. Secretagogues do not act as growth hormones at all as they stimulate the pituitary gland to secrete growth hormone.
Interestingly, the inconvenience of hGH injections first led to the discovery of Secretagogues. For years, it was believed that the pituitary gland, which produces growth hormones, dries up as a natural effect of aging. Science has recently discovered that growth hormones reside in the pituitary gland, which stops the release due to aging. Scientists then discovered that certain combinations of amino acids could actually spur the pituitary gland to release the growth hormones. Experiments soon led to the right combinations.
Natural secretagogue is the most practical approach because there are no side effects. In comparison with hGH, their potency and efficacy are low. Since these are orally taken, they can be a first line approach for those who may not choose hGH injections.
This category of hGH products uses amino acids as “secretagogues,” which stimulate the pituitary gland to produce hGH. Other proprietary agents are usually part of the powder/tablet mix, which provide each product with a presumed marketing advantage. Studies show that certain amino acid combinations such as L-lysine, L-arginine, L-ornithine and L-glutamine can stimulate pituitary hGH. While this is theoretically plausible and positive clinical results have been widely reported, published double blind controlled studies that show evidence that these other proprietary factors provide additional pituitary hGH secretion is still incomplete at best. Most studies reveal at least two grams of amino acids are needed to have any effect on pituitary hGH stimulation.
Glutamine is the most abundant amino acid in the body and causes GH secretion. It is a conditional amino acid as the body may not be able to synthesize it under stressful conditions. Traditionally it has been used to strengthen the immune system. The standard anti-aging intake is 50 mg to 1 gm twice daily.
Glutamine is a neurotransmitter in the brain. It is essential for proper brain functions, immune functions, kidneys, pancreas, bladder, and liver functions.
Glutamine becomes one of our body’s most powerful antioxidants in high quantities. Many people, especially those in weight training, add this amino acid due to its benefit in muscle metabolism. Supplementation of two to three gm/day is quite common. For those who plan to take extra doses, it is best to divide the doses throughout the day with up to four servings daily.
Two grams of glutamine was shown to cause a four fold increase in Growth Hormone levels.
Lysine is an essential amino acid, which affects bone formation, height, and genital function. It also boosts the effects of arginine. The recommended dosage is one gram on an empty stomach one hour before bedtime and before exercise.
Ornithine is a non-essential amino acid. It is used to potentate the effect of Arginine. The suggested dosage is one gram at bedtime. Doses of more than two to five grams have been known to cause diarrhea.
C. Oral Peptide Secretagogues
hGH is a hormone made up of a long chain of amino acids. Only a portion of the long chain of amino acids makes up the active ingredient. Researchers have been able to identify and extract these active peptides, which are usually five to ten amino acids linked together in a chain. These are then stabilized and formulated into a power or tablet effervescent form. The oral tablets are dissolved in water to be taken before bedtime on an empty stomach. This is to stimulate the release of hGH from the anterior pituitary, which peaks during the early phase of sleep. The effervescent form is best to draw the peptide away from the gastric juice closer to the mucous for better absorption. Gastric juices are highly acidic. Peptides are proteins that are easily denatured when exposed to an acidic environment. Extraction of the peptide is a tedious process. Peptides are not stable enough to maintain its activity in an aqueous environment. Thus, the peptide is formulated in the oral tablet format. Secretagogues using peptides are abundant in the marketplace. They are sold as a natural nutritional supplement and no FDA approval is required. However, some unscrupulous operators simply use ground bovine pituitary gland and pass them off as secretagogues. The consumer is often faced with the arduous task of identifying which is the real secretagogue.
Secretagogues can also work at multiple sites leading to growth hormone release. For example, a secretagogue targeted towards the hypothalamus would stimulate the hypothalamus to release Growth Hormone Releasing Factor (GHRF) that in turn stimulates the pituitary gland to release growth hormone. An oral peptide pituitary secretagogue, on the other hand, stimulates the pituitary gland directly to effect the release of growth hormone.
An effective secretagogue could easily raise IGF-1 levels, although the result is not as significant as growth hormone injections. Clinically many users have reported better sleep, increased alertness during the day, and less joint pain.
IGF-1 levels may not be the best indicator of how effective a secretagogue is for the GH receptor sites may be damaged. A low IGF-1 level does not mean that the body’s growth hormone level has not increased. It may simply mean that that the level is not accurately measured, or that there is a defective receptor site. If your IGF-1 does not increase, do not be despair. Talk to your health care practitioner. How you feel is just as important and sometimes even more important than laboratory studies alone.
D. Growth Factors
Growth factors (GF) are small protein chains, commonly known as polypeptides, which bind to cell surface receptor sites and exert actions directly on the target cells. This is generally done through cellular proliferation and or differentiation.
Some GFs exert generalized effect, while others are cell and action specific. There are many different classes of GFs. Some common ones include: Insulin-like Growth Factor (IGF-1) that is responsible for much of Growth Hormones (GH) action in the body; Interleukins (IL); Fibroblast Growth Factors (FGF); Transforming Growth Factor (TGF); Tumor Necrosis Factor (TNF); Epidermal Growth Factor (EGF); and Transforming Growth Factors-b (TGFs-b).
GFs come from a wide variety of sources. Epithelial Growth Factors (EGF) comes from sub maxillary gland, and FGF comes from a wide range of cells. A unique family of growth factors that is secreted primarily by leukocytes (white blood cells) is called cytokines. When such cytokines are secreted by lymphocytes, they are called lymphokines. Many of the lymphokines are also known as interleukins (ILs). Not only are interleukins secreted by leukocytes, they are also able to affect the cellular responses of leukocytes.
What Do Growth Factors Do?
Different GFs have different jobs to do. Generally, all of them work at the cellular level to:
Repair damaged cells
Enhance cellular proliferation
Maintain optimum function of the target organ
Rejuvenate aging tissues
While hormones generally are more specific and sometimes work through other mediations elicited from its simulation of intermediate organs, GFs often act directly on the target tissue and have a wide range of effects. Its action is mostly stimulatory. It can also work synergistically with other GFs or hormones to elicit a biological effect. Growth hormone, for example, exerts its effect in the body via Insulin-like Growth Factor (IGF-1). In other words, it is the IGF-1 that actually carries out the function of growth hormone and not growth hormone itself.