In a 1988 study of six men, GH came in about 6 daily pulses when fed, 10 after a 5-day fast
Peripheral Actions
GH acts on many tissues directly
The liver produces IGF-1 in response
Negative feedback loops exist
Peptide Interaction Points
GHRH Analogs (CJC-1295, Sermorelin)
Mimic natural GHRH at its pituitary receptor
Sermorelin, formerly FDA-approved as Geref, hasn't been marketed under that name in the US since 2008. In 11 older men, 6 weeks of nightly use raised overnight GH but not IGF-1
CJC-1295 with DAC lasts about a week in the blood. In 2006 single-dose trials, GH stayed raised for 6+ days and IGF-1 for 9-11 days; no trial measured muscle or fat
GH Secretagogues/GHRPs
Bind the ghrelin receptor (GHS-R1a)
Work through a different pathway than GHRH
In a 2-year trial in older adults, oral MK-677 raised IGF-1 and fat-free mass but not strength; fasting glucose rose
Synergistic Effect
Infusion studies in men show GHRH plus a GHRP releases far more GH than either alone; a 2009 study found the synergy shrinks with age and abdominal fat. No controlled trial has tested the common Mod GRF 1-29 plus ipamorelin stack.
Pathway Diagram
Hypothalamus: GHRH (+), somatostatin (-)
Stomach: ghrelin (+) via the receptor GHRPs use
Pituitary: GH released in pulses
Liver: IGF-1 made
Feedback: GH and IGF-1 damp release
Downstream Effects of GH
Direct GH Effects
Lipolysis: breaks down fat for energy
Protein synthesis: supports muscle maintenance
Glucose regulation: opposes insulin
Bone health: supports bone remodeling
IGF-1 Mediated Effects
Muscle growth: carries much of GH's anabolic signal, though trials above saw no strength change
Cell proliferation: tissue growth and repair
Satellite cell activation: shown mainly in animals
Feedback Mechanisms
Negative Feedback
GH and IGF-1 inhibit further GH release
Acts on hypothalamus and pituitary
Peptide Advantages
Work within natural feedback systems
Preserve pulses: in a 2006 study, CJC-1295 raised trough GH 7.5-fold while pulse frequency and size were unchanged, contradicting the forum idea of a GH "bleed"
Timing and GH Pulses
Natural GH Pattern
Largest pulses come in deep sleep; both decline by midlife in men
Smaller pulses throughout day
Exercise triggers release
Fasting enhances secretion
Optimizing with Peptides
Users commonly describe three timings; none has been tested with peptides:
Morning fasted: low glucose, on the theory of a bigger response
Post-workout: adding to exercise GH
Pre-bed: matching the sleep pulse (sermorelin trials dosed nightly)
Individual Variation
Factors Affecting Response
Age (GH declines with age)
Body composition
Sleep quality
Stress levels
Baseline hormone status
Why Response Varies
Receptor density differs
Somatostatin tone varies
Pituitary capacity differs
IGF-1 production varies
Implications for Bodybuilders
Maximizing GH Response
Many users avoid carbohydrate before injecting; untested
Combining GHRH and GHRP is common practice
Understanding Limits
Can't exceed pituitary capacity
Natural feedback still operates
As of October 2026, WADA prohibits GHRH analogs and GH secretagogues at all times (S2.2.4)
