Growth hormone is the pituitary signal that tells the body to grow in childhood and to repair and rebuild in adulthood. Most of its effects are indirect — it drives the liver to produce IGF-1, and IGF-1 does most of the visible tissue work. It is released in pulses, mostly at night and during exercise, and its biology has been poorly served by the cottage industry of "anti-aging" clinics that built themselves on a misread of a 31-year-old paper.
At a glance
What it does
In children and adolescents, growth hormone drives linear bone growth by acting on the growth plates via IGF-1, along with a long list of systemic growth effects on muscle, organ, and connective tissue. Children with severe GH deficiency are short and under-muscled; children with excess GH (rare, usually pituitary adenoma) develop gigantism. Both are corrected if caught before growth plates close.
In adults, linear growth is over — growth plates have fused — but GH continues to do work. It promotes lipolysis, driving free fatty acid release from adipose stores and contributing to overnight fuel balance during sleep. It supports protein synthesis and lean body mass, especially in the context of tissue repair after injury or training. It is a glucose counter-regulatory hormone, opposing insulin by reducing peripheral glucose uptake and increasing hepatic glucose production; this is part of why chronic GH excess produces insulin resistance.
GH also maintains the mineral balance and collagen matrix of bone, supports cardiac muscle, and modulates immune function. Adults with untreated GH deficiency (usually from pituitary injury or tumor) show reduced lean mass, increased visceral fat, reduced bone density, poor exercise capacity, reduced quality of life, and elevated cardiovascular risk — a real syndrome that resolves with replacement.
Most of what GH does in tissues is mediated indirectly through IGF-1. GH hits liver, liver pumps out IGF-1, and IGF-1 drives the growth and repair work in muscle, bone, and connective tissue. Some GH effects — particularly lipolysis and counter-regulation of insulin — happen directly through the GH receptor without the IGF-1 intermediary. Serum IGF-1 is the more stable and interpretable lab because it integrates pulsatile GH over about 24 hours; random GH levels tell you almost nothing without context.
How it works
Growth hormone is made by somatotroph cells in the anterior pituitary and released in pulses under control of two opposing hypothalamic signals: GHRH stimulates release, somatostatin inhibits it. The pattern is sharply pulsatile, with most adult GH secretion occurring in 3-5 major pulses per 24 hours, mostly during deep (slow-wave) sleep in the first half of the night. High-intensity exercise produces additional daytime pulses. Ghrelin, the stomach-derived hunger hormone, is also a potent GH secretagogue via the GHS-R receptor — the pathway exploited by synthetic GH secretagogues.
GH binds receptors on hepatocytes, adipocytes, myocytes, and chondrocytes, signaling through JAK2 and STAT5 to drive IGF-1 transcription plus direct effects on fuel mobilization. IGF-1 circulates bound to IGF-binding proteins (mostly IGFBP-3) and acts at IGF-1 receptors on target tissues. IGF-1 and GH both feed back on the hypothalamus and pituitary; glucose, free fatty acids, cortisol, thyroid, estrogen, and sex steroids all modulate the setpoint.
Levels & ranges
Random serum GH in adults typically runs under 5 ng/mL in the fasted daytime state, but pulses push it up to 30 ng/mL or higher transiently, especially at night. Because of the pulsatility, a single random GH value is usually uninterpretable. Clinically meaningful testing relies on dynamic tests — GH stimulation (insulin-tolerance, arginine, glucagon, or macimorelin) to probe deficiency, and glucose suppression (oral glucose tolerance test) to probe excess.
Serum IGF-1, measured against an age- and sex-specific reference range, is the workhorse integrated measure. Normal adult ranges span roughly 115-350 ng/mL at age 20-40, declining steadily with age. A low IGF-1 in the context of clinical suspicion supports GH deficiency; an elevated IGF-1 supports acromegaly pending confirmation by failure of GH to suppress after oral glucose. Serum IGF-1 declines about 14% per decade after 30, reaching perhaps a third of young-adult levels by 70 — a normal feature of aging, not a "deficiency" to treat.
When it goes wrong
Pediatric GH deficiency, untreated, produces short stature and delayed bone age. Recombinant human GH (rhGH) normalizes growth if started early. Indications include confirmed GH deficiency, Turner syndrome, Prader-Willi syndrome, idiopathic short stature, and SHOX deficiency. The older practice of extracting GH from cadaver pituitaries was stopped in the 1980s after Creutzfeldt-Jakob disease was traced to contaminated batches.
Adult GH deficiency is usually from pituitary injury — tumor, surgery, radiation, traumatic brain injury, autoimmune hypophysitis, or Sheehan's syndrome. Symptoms include increased visceral fat, reduced lean mass, reduced bone density, poor exercise tolerance, dyslipidemia, and reduced well-being. Daily subcutaneous rhGH restores body composition and quality-of-life measures, though the mortality benefit is still debated.
Acromegaly is GH excess in adults, almost always from a pituitary adenoma. Symptoms evolve over years: coarsening of facial features, enlarged hands and feet, arthralgia, sweating, jaw prognathism, plus systemic effects — insulin resistance, hypertension, sleep apnea, cardiomyopathy, colorectal polyps. Diagnosis hinges on elevated IGF-1 and failure of GH to suppress after oral glucose. Treatment is transsphenoidal surgery when possible, with somatostatin analogues, pegvisomant, or radiation as second-line. Untreated acromegaly shortens life by roughly a decade; treated acromegaly normalizes mortality.
Age-related decline in GH and IGF-1 (somatopause) is real but is not a pathological deficiency. Treating otherwise-healthy older adults with rhGH for "anti-aging" does not produce durable benefit and carries real risks (glucose intolerance, edema, joint pain, carpal tunnel, and possible acceleration of subclinical cancers). The FDA prohibits rhGH marketing for anti-aging for exactly this reason.
Interactions
Sleep is the single largest physiologic lever on endogenous GH. Most adult GH secretion happens during deep slow-wave sleep in the first few hours of the night. Chronic sleep deprivation and poor sleep quality substantially reduce 24-hour GH output. Shift work and repeated short sleep weeks show measurably lower IGF-1 over time.
Heavy resistance training and short-interval sprints produce acute GH spikes. Whether these spikes matter beyond the broader training effect on muscle and metabolism is uncertain — the literature generally finds the acute spike matters less than sustained training.
Insulin and GH are physiologic antagonists. Chronic hyperinsulinemia (obesity, insulin resistance, type 2 diabetes) suppresses GH secretion, which is part of why weight loss often raises GH and IGF-1 without any exogenous intervention. Conversely, acromegaly drives insulin resistance and often clinical diabetes.
Pharmacologic manipulation includes direct rhGH injection (daily subcutaneous, with weekly formulations like somapacitan approved for adult GHD), GHRH analogues (sermorelin, tesamorelin — the latter FDA-approved for HIV-associated lipodystrophy), and GH secretagogues (ipamorelin, GHRP-2/6, and long-acting CJC-1295, commonly paired in grey-market peptide stacks). Secretagogues preserve pulsatility and feedback in ways direct rhGH does not — a theoretical advantage; the clinical evidence in non-deficient adults is thin, and grey-market sources are unregulated.
Oral estrogen raises GH but blunts IGF-1 by inducing hepatic GH resistance. Women on oral estrogen generally show higher GH and lower IGF-1 than otherwise comparable men.
Honest take
Rudman 1990 is the paper that launched the anti-aging GH industry and is probably the most misread paper in modern endocrinology. Twenty-one older men got GH for six months, gained some lean mass and lost some fat. The study was never blinded, never controlled for exercise or diet, and never followed long enough to see side effects stabilize. The NEJM editor published a clarifying letter in 2003 explicitly warning that the paper did not support anti-aging use. That warning did nothing to slow the clinics. The current honest position: genuine GH deficiency in children or adults (confirmed by proper dynamic testing) is a real indication for real GH replacement, and the clinical benefit is substantial. Using rhGH or its secretagogues for "anti-aging" in otherwise-healthy older adults has not produced durable benefit in controlled studies and has produced predictable side effects — glucose intolerance, edema, arthralgia, and a real concern about promoting subclinical malignancy. The grey-market peptide scene around CJC-1295, ipamorelin, and similar compounds is unregulated, often contaminated, and pretends that "secretagogue, not GH itself" is a safety claim. It is not. If you have IGF-1 well below your age range and symptoms that fit adult GHD, see an endocrinologist. If you just want to feel younger, build muscle, and lose fat, the evidence says sleep, lift, eat appropriately, and stop shopping for a GH clinic.
Sources
- Rudman et al., NEJM (1990) — the original paper on GH in older men, notable as much for what it did not show as for what it did.
- Molitch et al., Endocrine Society Clinical Practice Guideline — diagnosis and treatment of adult growth hormone deficiency.
- Katznelson et al., Endocrine Society Clinical Practice Guideline — diagnosis and treatment of acromegaly.
- Liu et al., Annals of Internal Medicine (2007) — systematic review on GH in healthy elderly adults finding minimal benefit and meaningful harm.
- Veldhuis et al., Journal of Clinical Endocrinology and Metabolism — on the pulsatile physiology of GH secretion, sleep dependence, and age-related decline.