Medical Research

Growth Hormone Synthesis, Storage, Secretion and Decline

Human Growth Hormone is a protein consisting of 191 amino acids that is synthesized, stored and secreted by specialized cells called somatrophs in the anterior pituitary gland where it is stored in large dense granules that can account for a significant portion of the dry weight of the pituitary. Growth hormone secretion peaks in adolescence when accelerated growth occurs and then declines with age. Although the body still synthesizes nearly the same amount of GH, the amount released from the pituitary falls steadily with advancing age. After age 30 growth hormone blood levels decline about 10% to 14% per decade. Between 40 to 50 years of age growth hormone levels are only 50 to 60% of what they were at age 20.

At some point in life growth hormone secretion falls below the minimal maintenance level needed by the cells for reproduction and rejuvenation and the body begins to lose muscle, gain fat and the size and function of the organs falls. Decreased growth hormone secretion or reduced GH activity occurs in everyone as they age and is accompanied by the so-called symptoms of aging. GH secretion is reduced in postmenopausal women and aging males because of excessive release of hypothalamic somatostatin and by the impact of a decline in sex hormones.

Even though GH is manufactured and secreted into the bloodstream by the pituitary, GH release is controlled by two specialized peptides secreted by the hypothalamus. Growth Hormone releasing hormone (GHRH) stimulates release (secretion), while somatostatin, the natural inhibitor of growth hormone, inhibits its release. Over the last two decades, other peptides of different sizes and structures have been synthesized by researchers, which are also able to influence GH secretion. These peptides, known as growth hormone releasing peptides (GHRPs), are able to selectively stimulate GH release when given orally. GHRP’s have receptor sites both on the hypothalamus and the pituitary. Research has shown that somatostatin levels rise with age and that when somatostatin production is eliminated in animal experiments, GH production in older animals is as great as young animals. Clinical research indicates that the pituitary glands of older mammals continue to synthesize adequate levels of growth hormone all through life, but that problems with inadequate stimulation of pituitary secretion of GH, increased levels of secretion inhibitors and problems with reduced sensitivity of growth hormone receptors interfere with GH activity.

The hypothalamus, by regulating pituitary secretion, controls both basal and episodic secretion of growth hormone (GH), as well as the secretion of other anterior pituitary hormones such as prolactin, adrenocortropin, follicle stimulating hormone, luteinizing hormone, and thyroid stimulating hormone.

GHRH is a peptide secreted by the hypothalamus. GHRH upon reaching anterior pituitary cells binds to special transmembrane GHRH receptors on pituitary (somatotroph) cells activating GH gene transcription, GH synthesis and GH release. Ordinarily a decline in GH and IGF-1 tells the hypothalamus to release more GHRH causing the pituitary to make and secrete more growth hormone, but this feedback loop breaks down with age when somatostatin levels and blood glucose levels rise.

Somatostatin is another peptide secreted by the hypothalamus, it binds to receptors on pituitary (somatotroph) cells and it inhibits the secretion of GH. Somatostatin is found both in the hypothalamus of the brain and in the organs of the gut. The somatostatin secreted by hypothalamic neurons inhibits GH release from anterior pituitary cells. Gastrointestinal somatostatin secreted by the stomach, pancreas and intestines also inhibits the release of a number of gastrointestinal and pancreatic hormones. GHRH and somatostatin release are controlled by blood concentrations of GH, IGF-1 and blood glucose. When GH, IGF-1 or blood glucose levels reach too high a concentration in the bloodstream GHRH secretion falls and somatostatin secretion rises, the end result is that GH release from the pituitary is shut down. From this mechanism it can be seen that use of GH injections that raise GH levels in the blood, elevated levels of blood glucose or use of amino acid stackers that raise IGF-1 levels dangerously high may eventually result in a fall in pituitary secretion of GH.

Besides GHRH and somatostatin several other factors also influence GH secretion including the female hormone estradiol as well as glucose and insulin levels in the bloodstream. When blood sugar levels rise too high, because of age or disease related changes in cell response to insulin, GH secretion is inhibited. A Science-based GH formula can begin to address the problem of age related rises in blood glucose and insulin by incorporating Novel Polyose Complex in the formula. Novel Polyose Complex is designed to both regulate insulin levels and improve absorption of the other active ingredients.

The endocrine system is a tightly controlled system since only very small amounts of the biological response modifiers (hormones) secreted by the endocrine glands are needed to exert physiologic effects. The endocrine system is controlled by feedback circuits, which for the most part are negative feedback loops.

Negative feedback occurs when the output of a pathway inhibits inputs to the pathway. The body uses feedback loops in order to regulate secretion of growth hormone in the hypothalamic-pituitary axis. Growth hormone-releasing hormone, together with somatostatin, control release of growth hormone (GH) from growth hormone producing cells (somatotropes) in the anterior pituitary.

When growth hormone levels fall too low, the hypothalamus produces and releases growth hormone releasing hormone to stimulate the pituitary to increase secretion of growth hormone. When growth hormone activity is determined by the body to be too high the hypothalamus produces and releases somatostatin to cause the pituitary to secrete less growth hormone. This process is similar to the way people drive their cars. When a person determines he is going too slow he or she will step on the accelerator and conversely when he or she determines they are going too fast they will step on the brakes.

As a consequence of the feedback controls that govern growth hormone concentrations in the blood and the fact that growth hormone has a limited lifespan or half-life, growth hormone is secreted in pulses. In fact virtually all hormones have a pulsatile pattern of secretion. Variations in GH pulse characteristics reflect specific physiologic states such as sleep-wake cycles, blood glucose and fatty acid levels, and exercise. GH is released in bursts throughout the day with the highest secretion during the first 90 minutes of sleep. Since GH has a very short half-life, GH levels in the blood fall about 50% within 20 minutes of release into the bloodstream. When a burst occurs, peak GH levels in the blood may rise 100-fold greater than baseline.

Weight-resistance training also can increase GH release from the anterior pituitary cells by promoting release of growth hormone releasing hormone. Plasma GH levels increase with exercise intensity. Because blood glucose is used by the muscles during exercise, blood glucose levels could fall dangerously low if the body did not have compensatory mechanisms to conserve blood glucose for tissues like the brain, which uses blood glucose as its only fuel. Thus the GH acts to conserve blood glucose and provide an alternative energy source for the skeletal muscles and the heart by increasing fat mobilization from fat stores so that fat can be burned as fuel. This mechanism maintains energy production in the muscles and the heart when tissue glycogen levels and blood glucose levels begin to fall during prolonged exercise. The fact that GH mobilizes and increases fat burning is the reason GH therapies promote weight loss.

Once GH enters the bloodstream, some goes to the tissues where it activates GH receptors on the cell membranes initiating a series of cellular reactions. In addition some of the GH is converted by cells of the liver and bone to an active metabolite - IGF-1, which then initiates cellular responses when it binds to its own receptors on the cell membranes.

Studies have shown that both GH and IGF-1 have some similarities in biological activity, but GH also performs other additional biological actions that IGF-1 is unable to perform. This means that GH supplements that only raise IGF-1 levels, but not GH levels or do not restore GH receptor sensitivity are incomplete in their GH effects. Because, in aging, not only does GH secretion fall, but also GH receptors become desensitized. If the cell receptors are damaged or desensitized GH and IGF-1 are ineffective even if adequate amounts are present. GH cell receptor sensitivity not only declines with age, but GH cell membrane receptor sites can also be blocked by environmental toxins and desensitized by elevated insulin levels.

Recognition of the factors that determine GH secretion, GH control mechanisms, and GH control mechanism dysregulation should be taken into account by individuals who choose a GH enhancement agent like a science-based formula for growth hormone rebalancing as opposed to GH replacement agents like GH injections. A science-based GH therapy can support GH activity by normalizing GH release, IGF-1 production, and GH cell receptor re-sensitization.



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