Relationship between growth hormone and igf 1 does it work

relationship between growth hormone and igf 1 does it work

IGF-1 is crucial for growth through clarifies the relationship between nutrition and IGF Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a protein that in humans is encoded by the IGF1 gene. IGF-1 has also been referred to as a " sulfation factor" and its effects were termed "nonsuppressible insulin-like activity" (NSILA) in the s. IGF-1 is a hormone similar in molecular structure to insulin. IGF-1 binds to IGFBP-3 in a molar ratio. In short, IGF-1 acts as the principal mediator of growth hormone's anabolic effects . Whilst growth hormone (GH) is capable of acting directly upon receptors at its.

Although the precise function of this ultradian pattern remains unknown, the pulsatile nature of growth hormone release has been confirmed in every species examined to date and appears to be essential to optimize biological potency of the hormone.

relationship between growth hormone and igf 1 does it work

The regulation of these pulses involve at least two hormones released by the hypothalamus; growth hormone-releasing hormone GHRH which increases growth hormone release [7,8] and somatostatin which inhibits its release [9]. The dynamic interactions between these hormones are responsible for high amplitude, pulsatile growth hormone secretion.

It is generally believed that somatostatin tone is dominant during trough periods, whereas when somatostatin is suppressed, growth hormone is released in response to secretion of GHRH [10].

Once growth hormone is secreted from the anterior pituitary, it binds with high affinity to the growth hormone receptor which is found in tissues throughout the body. Plasma growth hormone is carried by a binding protein which is homologous to the cleaved extracellular domain of the growth hormone receptor [11]. The growth hormone molecule exhibits two binding sites for the growth hormone receptor resulting in dimerization of the receptor, a step that is required for biological activity of the hormone [12].

Activation of the growth hormone receptor stimulates the synthesis and secretion of insulin-like growth factor-1 IGF-1a small peptide about 7. Although most of the circulating IGF-1 is derived from liver, growth hormone may also have a role in regulating the synthesis and secretion of IGF-1 from many tissues, thereby directly influencing the paracrine or local activities of the hormone [14—17]. IGFBPs function to regulate the availability of IGF-1 to its receptor in target tissues [18]and specific proteases are required to cleave the IGF-1 protein from its binding protein complex.

JERRY BRAINUM on Growth Hormone and IGF1

Once IGF-1 binds to the type 1 IGF receptor, it initiates autophosphorylation of the receptor, IRS-1 insulin receptor substrate phosphorylation, and tyrosine phosphorylation. Subsequent studies revealed a loss of nocturnal surges of growth hormone [22] and a decrease in plasma IGF-1 that paralleled the decline in growth hormone pulses [23,24]. These early studies in humans have been confirmed by numerous investigators see review by Corpas et al.

Shortly after the documentation of decreases in growth hormone secretion in aged humans, studies confirmed that the amplitude of growth hormone pulses also decreased with age in rodents [25] see Fig. These studies immediately progressed to an investigation of the mechanisms responsible for the decline in growth hormone secretion.

relationship between growth hormone and igf 1 does it work

Several studies in both humans and animals documented a decreased in vivo pituitary response to GHRH with age [27—29]. However, over the next several years, numerous studies attempting to detail the deficits within the pituitary gland produced controversial results which ultimately were attributed to either differential responses of older animals to the pharmacological agents used to suppress endogenous growth hormone pulses during in vivo testing [30] or to technical limitations involved with culturing anterior pituitary cells from older animals [31].

Our laboratory has found that older animals release increased amounts of somatostatin peptide from pituitary extracts, suggesting an age-related increase in the release of this peptide from hypothalamic neurons [34].

These results provided compelling evidence that increased somatostatin tone may be an important factor in the decline in growth hormone pulses with age. These conclusions were supported by research demonstrating that administration of cholinergic agonists or arginine, considered to preferentially inhibit somatostatin release, was capable of restoring growth hormone secretion in the elderly [34,35].

Although these studies did not address the synthesis and release of GHRH, a decline in this hormone is another contributing factor in the decrease in growth hormone secretion with age. GHRH mRNA decreases with age [36] and the feedback relationship between growth hormone and hypothalamic neurons is impaired [37].

Insulin-like growth factor 1

As a result, it was concluded that deficiencies within the hypothalamus involving regulation of both GHRH and somatostatin are responsible for the decrease in growth hormone secretion with age. In rodents, a two-fold increase in growth hormone receptors has been observed with age but this increase fails to compensate for the reduction in growth hormone secretion [39,40].

Growth hormone is made in the anterior pituitary gland, is released into the blood stream, and then stimulates the liver to produce IGF IGF-1 then stimulates systemic body growth, and has growth-promoting effects on almost every cell in the body, especially skeletal musclecartilageboneliverkidneynerveskinhematopoieticand lung cells.

Its primary action is mediated by binding to its specific receptor, IGF1R, which is present on the surface of many cell types in many tissues. Binding to the IGF1R initiates intracellular signaling. IGF-1 is one of the most potent natural activators of the AKT signaling pathwaya stimulator of cell growth and proliferation, and a potent inhibitor of programmed cell death. IGF-1 activates the insulin receptor at approximately 0. A key pathway is regulated by phosphatidylinositol-3 kinase PI3K and its downstream partner, the mammalian target of rapamycin mTOR.

As the name "insulin-like growth factor 1" implies, IGF-1 is structurally related to insulin, and is even capable of binding the insulin receptor, albeit at lower affinity than insulin. One such disorder, termed Laron dwarfism does not respond at all to growth hormone treatment due to a lack of GH receptors.

As a result, these patients cannot be expected to respond to GH treatment. People with Laron syndrome have strikingly low rates of cancer and diabetes.

Insulin-like growth factor 1 - Wikipedia

A number of disorders may increase the pituitary's GH output, although most commonly it involves a tumor called pituitary adenomaderived from a distinct type of cell somatotrophs.

It leads to anatomical changes and metabolic dysfunction caused by elevated GH and insulin-like growth factor 1 IGF-1 levels. As levels do not fluctuate greatly throughout the day for an individual person, IGF-1 is used by physicians as a screening test for growth hormone deficiency and excess in acromegaly and gigantism.

Interpretation of IGF-1 levels is complicated by the wide normal ranges, and marked variations by age, sex, and pubertal stage. Clinically significant conditions and changes may be masked by the wide normal ranges. Sequential management over time is often useful for the management of several types of pituitary disease, undernutrition, and growth problems.