Insulin-like growth factors (IGFs) are proteins structurally similar to insulin. Insulin-like Growth Factor-1 (IGF-1), a polypeptide hormone, significantly regulates normal growth and development throughout life. It is especially pronounced during rapid growth periods like childhood and adolescence, facilitating tissue expansion.
The Growth Hormone and IGF Connection
The production and regulation of IGF-1 are intricately linked to the growth hormone (GH) system, forming the GH-IGF-1 axis. This regulatory pathway begins in the pituitary gland, which releases growth hormone into the bloodstream. GH then travels to various tissues, with the liver being a primary target.
Upon reaching the liver, GH signals cells to produce and release IGF-1. GH acts as the initial signal, with IGF-1 serving as the direct messenger carrying out growth-promoting instructions and many of the direct effects on growth and cellular processes. The system also includes a negative feedback loop where IGF-1 can signal back to the hypothalamus and pituitary, inhibiting further GH secretion to maintain balance. Its bioavailability is extended by specific binding proteins, particularly IGFBP-3, which increase its half-life from minutes to hours.
Primary Functions in the Body
Once released, IGF-1 exerts widespread anabolic, or building, effects throughout the body. It stimulates the growth of bones and various tissues by encouraging both an increase in cell size, known as hypertrophy, and an increase in cell number through cell division, or hyperplasia. IGF-1 also actively prevents programmed cell death, a process called apoptosis, contributing to tissue maintenance and repair.
During childhood, IGF-1 is a significant driver of linear growth and bone development, supporting the rapid expansion of the skeleton and other organs. In adults, its functions shift towards maintaining existing muscle mass and facilitating the repair of damaged tissues. This includes promoting protein synthesis, which is essential for muscle strength and recovery.
Insulin-like Growth Factor-2 (IGF-2), while sharing structural similarities with IGF-1, primarily functions during fetal development. It is crucial for fetal growth, contributing to overall fetal size and placental development. IGF-2 can interact with insulin receptors during this early stage, influencing the formation of adipose tissue.
The Role of IGF in Health and Disease
When IGF-1 levels deviate from their normal range, various health conditions can arise. Abnormally low IGF-1 can lead to conditions like Laron syndrome, a rare genetic disorder characterized by growth hormone insensitivity, resulting in very low or undetectable IGF-1. Other causes of low IGF-1 can include liver cirrhosis, malnutrition, or certain genetic defects affecting the GH-IGF-1 axis. Adults with significantly low IGF-1 may experience reduced bone density, decreased muscle mass, and altered lipid levels.
Conversely, consistently high levels of IGF-1 can also pose health risks. Conditions like acromegaly or gigantism result from excessive growth hormone and, consequently, elevated IGF-1. Gigantism occurs before bone growth plates fuse, leading to extreme height. Acromegaly develops in adults after fusion, causing enlargement of hands, feet, and facial features.
Beyond growth disorders, elevated IGF-1 levels have been linked to an increased risk of certain cancers. IGF-1’s normal function of promoting cell growth and inhibiting apoptosis can unfortunately also support the proliferation and survival of cancer cells. Studies have shown a positive association between higher circulating IGF-1 and increased risk for colorectal, breast, prostate, thyroid, and melanoma cancers. The relationship with aging is also complex, with IGF-1 levels naturally declining over time, a process sometimes referred to as somatopause. Research suggests a U-shaped relationship between IGF-1 levels and mortality risk, meaning both very low and very high levels can be associated with detrimental outcomes, particularly in older individuals.
Factors Influencing IGF Levels
Several lifestyle and biological factors influence IGF-1 levels within normal ranges. Nutrition plays a significant role, with adequate protein intake being particularly influential in maintaining healthy IGF-1 concentrations. Malnutrition, especially insufficient caloric or protein intake, consistently leads to a reduction in IGF-1 levels. Specific nutritional components, such as casein found in milk and the mineral zinc, have been shown to positively correlate with IGF-1 concentrations.
Physical exercise also modulates IGF-1 levels, with responses varying by type, intensity, and duration. Resistance training and high-intensity sprint exercises can acutely elevate IGF-1 concentrations. However, endurance exercise may sometimes lead to a decrease in IGF-1. Exercise’s impact is also influenced by age, gender, and fitness level.
Sleep patterns affect hormone regulation, and sleep deprivation has been shown to suppress circulating IGF-1 levels. IGF-1 levels naturally fluctuate throughout life, peaking during the pubertal growth spurt and gradually declining from early adulthood into old age.