What is Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3)?
Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) is the main carrier protein for two important growth hormones in the body: IGF-1 and IGF-2. Nearly 80% of all circulating IGFs are attached to IGFBP-3. It forms a three-part complex with:
- IGF-1 or IGF-2
- IGFBP-3
- Acid-Labile Subunit (ALS)
This complex protects IGFs from breaking down too quickly and controls how much IGF reaches tissues. IGFBP-3 plays a major role in growth, development, cell survival, metabolism, and overall hormone balance.
Doctors commonly use IGFBP-3 along with IGF-1 while diagnosing:
- Growth hormone deficiency
- Acromegaly or gigantism
- Delayed or rapid puberty
- Metabolic disorders
- Chronic illness affecting liver or nutrition
Where is IGFBP-3 Produced in the Body?
IGFBP-3 is produced in several parts of the body.
1. Liver – Main production site
The liver produces the highest amount of IGFBP-3 when it receives signals from Growth Hormone (GH).
2. Other tissues
Smaller amounts come from:
- Kidneys
- Immune cells
- Bone
- Muscle
Although produced in multiple places, the liver contributes the majority.
Main Functions and Importance of IGFBP-3
1. Transports IGF-1 and IGF-2
IGFBP-3 binds with IGFs and prevents them from breaking down too quickly, increasing their stability.
2. Controls IGF Release to Tissues
It works like a regulator, ensuring only the required amount of IGF reaches the cells.
3. Supports Growth and Development
By stabilizing IGFs, IGFBP-3 indirectly helps:
- Bone growth
- Muscle development
- Tissue repair
- Cell development
4. Improves Growth Hormone (GH) Evaluation
Measuring IGF-1 + IGFBP-3 together increases accuracy when diagnosing:
- GH deficiency
- GH excess (acromegaly/gigantism)
5. IGF-Independent Functions
IGFBP-3 also has direct functions unrelated to IGFs, including:
- Controlling programmed cell death (apoptosis)
- Regulating immune responses
- Helping maintain healthy cell growth
These functions make IGFBP-3 useful in metabolic and endocrine disorders.
Causes of Low IGFBP-3 Levels
Low levels usually point to hormonal, nutritional, or organ-related problems.
1. Growth Hormone Deficiency
Since GH stimulates IGFBP-3 production, low GH → low IGFBP-3.
2. Malnutrition or Chronic Illness
Poor nutrition, long-term illness, and muscle wasting reduce IGFBP-3.
3. Liver Disorders
The liver makes most of the IGFBP-3, so liver diseases significantly decrease its level.
4. Hypothyroidism
Low thyroid hormones slow metabolic activity and reduce IGFBP-3 production.
5. Natural Aging
IGFBP-3 levels steadily fall as part of normal aging.
Symptoms of Low IGFBP-3 Levels
In Children
- Slow growth
- Short height
- Delayed puberty
- Low energy
- Growth hormone deficiency features
In Adults
Low IGFBP-3 symptoms come from underlying GH deficiency:
- Fatigue
- Low muscle mass
- Increased body fat
- Poor bone health
- Low quality of life
If caused by disease:
Symptoms depend on the illness, such as:
- Jaundice (liver disease)
- Weight loss (chronic illness)
Causes of High IGFBP-3 Levels
1. Growth Hormone Excess
Seen in:
- Acromegaly (adults)
- Gigantism (children)
2. High IGF-1 Levels
Both hormones rise together in GH excess.
3. Puberty
During puberty, GH naturally rises → IGFBP-3 increases.
4. Pregnancy
Hormonal changes mildly increase IGFBP-3.
5. Rare Tumors
Some tumors produce GH or IGF-related proteins.
Symptoms of High IGFBP-3 Levels
In Children – Gigantism
- Rapid height growth
- Very tall stature
- Enlarged hands and feet
In Adults – Acromegaly
- Enlarged hands, feet, jaw
- Thickened skin
- Deep voice
- Joint pain
- Excessive sweating
- Widened facial features
Symptoms from Pituitary Tumors
- Severe headaches
- Vision problems
- Hormonal imbalance
Reference Ranges
Values depend on age and sex.
Children (8–12 years)
2.5 – 6.0 mg/L
Adults (20–40 years)
3.0 – 7.0 mg/L
Older Adults (>60 years)
2.0 – 4.0 mg/L
Always check individual lab reference ranges.
Sample Type
- Blood sample (serum)
- No fasting required
Test Preparation
- No fasting needed
- Inform doctor about GH therapy
- Thyroid, nutrition, and liver tests may also be ordered
- Children should mention growth pattern and puberty stage
When to Consult a Doctor
Consult a doctor if you notice:
In Children
- Slow height growth
- Extremely fast growth
- Delayed puberty
- Early puberty signs
- Not following growth chart
In Adults
- Fatigue
- Weak muscles
- Thickened hands or facial changes
- Difficulty fitting rings, shoes, or gloves
- Joint stiffness
General
- Liver disease symptoms
- Thyroid imbalance
- Pituitary tumor symptoms (vision issues, headaches)
Any abnormal IGFBP-3 test should be evaluated by an endocrinologist.
Important Word Explanations
- IGF-1 / IGF-2: Growth-related hormones controlled by GH
- ALS: Acid-labile subunit; forms a complex with IGFBP-3
- Acromegaly: GH excess in adults causing enlarged body parts
- Gigantism: GH excess in children causing extreme height increase
- GH Deficiency: Low growth hormone levels affecting growth and metabolism
- Carrier Protein: A protein that transports hormones in the bloodstream
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