Growth Hormone and IGF-1 Signaling
How growth hormone and IGF-1 are made and controlled, what the GH-IGF-1 axis does, and why higher levels are not automatically better for health.
Content last updated . This page has not been medically reviewed.
Evidence labels: established, mixed, insufficient evidence, no good evidence of benefit, evidence of harm.
The chain of signals
| Step | What happens |
|---|---|
| Hypothalamus | Growth-hormone-releasing hormone (GHRH) and somatostatin control GH release from the pituitary [1][2] |
| Stomach | Ghrelin is also an important GH secretagogue, a signal that prompts GH release [2] |
| Pituitary | Releases GH in pulses [3] |
| Liver and other tissues | GH stimulates hepatic IGF-1 and IGF-1 expression in tissues including the brain [2] |
| Feedback | GH and IGF-1 feed back to dampen further release [3] |
GHRH is a 44-amino-acid peptide, described as the primary regulator of pulsatile GH secretion, opposed by somatostatin. [1] The two regulators' exact roles in timing GH pulses are still debated. [1]
What can change GH levels
Sleep, nutrition, stress, age and sex all contribute to normal variation in GH. [3] GH is released in pulses, so one reading is a snapshot of a moving signal. [3] Ghrelin and GHRH are discussed in ghrelin and growth-hormone secretagogues.What GH and IGF-1 do
GH plays an essential role in growth after birth and in metabolism, through direct effects and through IGF-1. [3] Both hormones also act in the brain, and altered secretion or sensitivity has been proposed as a risk factor for several neurological and psychiatric conditions. Label: insufficient evidence of cause, since the review describes association and emerging roles. [2]Medical conditions
Disorders of the axis include GH deficiency, acromegaly and GH insensitivity syndromes. [3] These are diagnosed and treated by clinicians; this page is no guide to testing or treatment.Is higher better?
No. Three examples from the sources:- IGF-1 and death risk. A meta-analysis of 19 cohort studies (30,876 adults) found a U-shaped relationship: both low and high IGF-1, compared with middle levels, were linked to higher all-cause mortality (hazard ratios 1.33 and 1.23). [4] This is observational and shows association, not that changing IGF-1 changes survival.
- Diet, aging and cancer. Research on fasting and calorie restriction proposes that reducing GH and IGF-1 activity may partly explain effects on cancer in rodents, with the authors noting that alternating low and normal levels may be ideal. [5] Label: preclinical for the animal findings.
- GH in healthy older adults. A systematic review of 18 study groups found GH changed body composition (fat down about 2.1 kg, lean mass up about 2.1 kg) without a significant change in weight, and did not change bone density, but was linked to more soft-tissue swelling, joint pain, carpal tunnel syndrome and breast enlargement in men, and somewhat more diabetes or impaired fasting glucose. The review noted small studies and that using GH for anti-aging is not FDA-approved in the US. [6] Label: mixed. Body composition changed, but the review also found side effects, and a body-composition change is not the same as better health.
Frequently asked questions
Is growth hormone a peptide?
It is a protein hormone made by the pituitary. GHRH, a smaller regulator, is a 44-amino-acid peptide. [1]
What does IGF-1 do?
It is a growth factor stimulated by GH, made in the liver and other tissues including the brain. [2]
Is a higher IGF-1 level healthier?
Not according to a meta-analysis: both low and high levels were linked to higher mortality than middle levels in observational data. [4]
Do GH injections slow aging?
In a systematic review of healthy older adults, GH changed body composition but was linked to more side effects, and bone density did not change. [6]
Why do GH levels vary so much?
GH is released in pulses and is shaped by sleep, nutrition, stress, age and sex. [3]
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
Safety note
References
- Hypothalamic GHRH. Reviews in Endocrine and Metabolic Disorders 2025. Read 2026-10-22.
- Growth Hormone and IGF-1 Actions in the Brain and Neuropsychiatric Diseases. Physiology 2026. Read 2026-10-22.
- Growth hormone: Synthesis and regulation. Vitamins and Hormones 2026. Read 2026-10-22.
- Association between IGF-1 levels ranges and all-cause mortality: A meta-analysis. Aging Cell 2022. Read 2026-10-22.
- Nutrition, GH/IGF-1 signaling, and cancer. Endocrine-Related Cancer 2024. Read 2026-10-22.
- Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Annals of Internal Medicine 2007. Read 2026-10-22.