Originally Posted by einstein1905
Forms of Human Growth Hormone (HGH)
By David Leonardi, M. D.
INTRODUCTION
Growth Hormone is a polypeptide hormone. This means it is composed of a long chain of amino acids, 191 to be exact. Under normal physiologic conditions, growth hormone is secreted by the anterior pituitary gland. This is a gland that lies at the base of the brain in a bony cavity called the Sella Turcica. In addition to growth hormone, the anterior pituitary also secretes prolactin, thyroid stimulating hormone, luteinizing hormone, follicle stimulating hormone, and adrenal corticotropic hormone. The secretion of growth hormone by the pituitary gland is initiated by the hypothalamus, another gland in the brain that lies right next to the pituitary. The hypothalamus initiates growth hormone secretion by secreting growth hormone releasing hormone (GHRH); at the same time it stops secreting a growth hormone inhibitory hormone called somatostatin. When somatostatin is turned off and GHRH is turned on, the pituitary will release growth hormone in bursts of activity. These bursts of growth hormone release occur primarily during deep stages of sleep, such as stage 3 and stage 4. Once released in the blood, growth hormone is very short lived. It is generally completely metabolized and gone within a half-hour. During that time, however, it manages to reach the liver and many other cells in the body, and induce them to make another polypeptide hormone called Insulin-like Growth Factor One (IGF-1). It is really IGF-1 that travels around to the various tissues of the body to effect most of the benefits that we attribute to growth hormone. The secretion of growth hormone itself is regulated by a classic biofeedback loop. This means when levels of growth hormone in the blood reach a certain threshold, growth hormone stimulates receptors in the pituitary to stop further growth hormone secretion. It also stimulates receptors in the hypothalamus to stop GHRH and turn on somatostatin. IGF-1, which goes up in response to growth hormone, also feeds back on the pituitary and hypothalamus to help control growth hormone secretion. This is nature's system of checks and balances to assure we don't have too much of any one hormone.
NOMENCLATURE
The nomenclature for growth hormone is a bit complicated, but understanding it from the beginning can save much confusion in the future. Somatropin refers to growth hormone of the same amino acid sequence as the naturally occurring growth hormone. Somatropin extracted from the human pituitary gland was originally designated (hGH, or pit-hGH). Manufactured growth hormone is made by recombinant DNA technology. This is a system of genetically modifying either bacteria cells or mammalian cells in tissue culture so that they include in their genome, the gene that directs the cell to make human growth hormone. As the cells in the tissue culture grow and function, they will synthesize human growth hormone by the exact same process in the human pituitary. Since this is a natural process, human growth hormone is not considered a synthetic. The proper abbreviation for manufactured (recombinant) human growth hormone is rGH. Unfortunately, the abbreviations have been misused even in the medical community, and recombinant human growth hormone is commonly represented by the abbreviation hGH. The designation is no longer critical since human growth hormone of pituitary origin is no longer used in the United States, or anywhere in the world that I'm aware of. The term hGH or GH therefore, refers to human growth hormone from recombinant DNA technology. It is pure and 100% free of any contaminants or micro-organisms.
HISTORY
Prior to the advent of recombinant DNA technology, the only source of growth hormone was from human cadavers. More than 27,000 children worldwide were treated with growth hormone of this source (pit-hGH). Due to short supply, children were treated with low doses and interrupted regimens. As a result, their response and ultimate height was mitigated. Distribution of pit-hGH was stopped in the United States and most of Europe in 1985, with the emergence of Creutzfeldt-Jakob Disease. This is a rare and fatal spongiform encephalopathy, caused by a small pathogen called a prion. This is the same pathogen that causes "Mad Cow Disease" recently seen in Europe from infected cattle. It is impossible to catch Creutzfeldt-Jakob Disease or any other infection from recombinant human growth hormone because it is not derived from a human or animal source, but from a purified tissue culture. For purposes of this discussion, the term growth hormone, GH or hGH will mean growth hormone made by recombinant DNA technology.
The bio-potency of commercially available growth hormone is typically represented by either milligrams or units. To put it simply, 1 milligram of growth hormone is equivalent to 3 units. The international units were developed by the World Health Organization in order to standardize growth hormone preparations because of the various production techniques used early on in the manufacturing process. By now, the manufacturing process has been streamlined and largely perfected so the bio-equivalency of the various brands of growth hormone (at least those manufactured and approved by the FDA for sale in the United States) are identical. Therefore, a typical 15-unit vial of growth hormone contains 5 mg, and a 4-unit vial contains 1.33 mg.
USES OF GROWTH HORMONE
Growth hormone was initially used for children of short stature who are growth hormone deficient, either because of an inactive pituitary, a tumor of the pituitary, or destruction of the pituitary by surgery or by radiation to remove a tumor. The other pituitary hormones were replaced along with GH. Growth hormone was used only until the children reached an acceptable adult height and then it was stopped because it was thought to be useful only for growth. The other pituitary hormones, however, which were thought to be more critical, were continued throughout adulthood. It wasn't until much later that adult growth hormone deficiency was recognized to be a problem. It was discovered that adults who were deficient in growth hormone suffered from premature cardiovascular disease, reduced bone density, central obesity, decreased muscle mass, depressed mood, elevated levels of LDL (bad) cholesterol, slower wound healing, fatigue, poor exercise tolerance and poor immune function. At that point the use of growth hormone began in this unfortunate population, resulting in improvement of all of the above. It wasn't until 1990, however, that the benefits of growth hormone and the treatment of normal aging were recognized. The most recent new use of growth hormone is for the treatment of AIDS Wasting Syndrome. This is the condition of weakness, fatigue, and loss of muscle mass in AIDS patients. Since we at Cenegenics® specialize in metabolic and hormonal control of aging, we will limit this discussion to the use of growth hormone in the treatment of normal aging.
SOMATOPAUSE
Somatopause is an extrapolation of the term "menopause." Menopause is the condition in women whereby the ovaries atrophy and cease to produce the sex hormones Estrogen, Progesterone and Testosterone. Somatopause signifies the gradual decline in growth hormone production by the adult pituitary gland in both men and women that begins at approximately age 30 and continues at a steady rate throughout life. The decline in growth hormone level that occurs with Somatopause is accompanied by deterioration in the structure and functional capacity of our body, which is ultimately devastating to the human condition. In fact, there is absolutely no difference between the clinical signs and symptoms of aging and those of adult growth hormone deficiency described above. The late Dr. Daniel Rudman first described the benefits of growth hormone therapy in normal aging adults. Dr. Rudman published a landmark article in the New England Journal of Medicine on July 7th, 1990. In his article, Dr. Rudman showed that by putting healthy aging men on growth hormone for six months, he was able to decrease their body fat by 14.4%, increase muscle mass by 8.8%, increase skin thickness by 7.1%, and increase lumbar bone density by 1.6%. These exciting findings clearly inaugurated the movement to supplement growth hormone in healthy aging adults, which today is becoming commonplace.
TREATMENT REGIMENS
Growth hormone can be given either subcutaneously or by intra-muscular injection with equal therapeutic activity. Subcutaneous administration is now used almost exclusively because intra-muscular administration is fraught with an increase in side effects without any additional therapeutic benefit. Back in Dr. Rudman's time, growth hormone was typically dosed three times a week in what we now consider a high dose regimen. People would typically receive 12-18 units per week given in injections of 4-6 units, three times a week. Although great benefits were seen, side effects were very common, and much more bothersome than those we see today. Currently we use only about half the weekly dose used in Dr. Rudman's study, by smaller and more frequent injections, which provide both a better clinical response and far fewer side-effects. In one study on growth hormone deficient children, those that received daily injections increased their height during the study period by 9.7 centimeters more than those who received thrice-weekly injections. Besides the low dose-high frequency technique, the physicians at Cenegenics® also employ morning injections as opposed to evening. The reason for this has to do with the biofeedback mechanism for growth hormone. Most of our natural pituitary growth hormone secretion occurs at night during deep stages of sleep. Injecting growth hormone at night raises the serum level of growth hormone precisely during the time the pituitary is scheduled to become active. This high serum level of growth hormone from the injection can suppress our natural pituitary function by negative feedback. We then not only lose the benefit of our own endogenous growth hormone, but also run the risk of surpressing the pituitary, thus making it "lazy". For the most part, the pituitary has completed its function and is at rest by 5 a.m. Therefore injecting after awakening in the morning results in injecting "on top of the peak" of endogenous (our own) growth hormone, so as not to suppress the pituitary. By the time the pituitary is ready again for its nighttime activity, the growth hormone given in the morning injection has been completely metabolized. This eliminates the risk of pituitary suppression.
