ACTH · Corticotropin · Adrenocorticotropic Hormone
ACTH 1-39 is the full 39-amino-acid sequence of adrenocorticotropic hormone (corticotropin), the pituitary peptide that stimulates the adrenal cortex to produce cortisol and other glucocorticoids. The synthetic 1-39 sequence is functionally equivalent to native human ACTH. The shorter cosyntropin (ACTH 1-24) retains full adrenal-stimulating activity and is the standard diagnostic agent for adrenal function testing (the 'cortrosyn stim test'). H.P. Acthar Gel (porcine ACTH analog, repository corticotropin injection) is FDA-approved for infantile spasms and select autoimmune conditions.
Diagnostic: 0.25mg cosyntropin IM/IV at 8 AM, baseline cortisol drawn before, 30 and 60 min after. Clinical Acthar Gel: per neurology / rheumatology specialist.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
ACTH binds the melanocortin-2 receptor (MC2R) on adrenal cortex cells, primarily in the zona fasciculata. Activation of MC2R via Gs/cAMP/PKA triggers the steroidogenic cascade - cholesterol mobilization, StAR protein upregulation, and downstream P450 enzyme activity producing cortisol, corticosterone, and to a lesser extent aldosterone and adrenal androgens.
Primary effect. Plasma cortisol rises within 30-60 minutes of ACTH administration; baseline cortisol restored over 4-8 hours.
ACTH shares N-terminal sequence with α-MSH and can stimulate MC1R on melanocytes - explains the hyperpigmentation seen in chronic ACTH excess (Addison's disease patients on cortisol replacement, or pituitary ACTH-secreting tumors).
Modest DHEA stimulation alongside cortisol - relevant in adrenal androgen replacement contexts.
Acute ACTH stimulation distinguishes primary adrenal insufficiency (failed cortisol response) from secondary adrenal insufficiency (preserved or partial response) - the standard cosyntropin stim test.
Sustained ACTH elevation produces Cushing-like syndrome - central obesity, glucose dysregulation, hypertension, muscle wasting, mood changes, immunosuppression. This is why ACTH is not used as a tonic peptide in fitness contexts.
Acute cortisol rise within 30-60 min of dose.
Days-weeks of repeated dosing produces glucocorticoid effects.
Chronic dosing produces iatrogenic Cushing syndrome.
Each reference below was re-fetched from its PubMed record, and the quoted sentence was confirmed to appear in that abstract and to support the claim it sits under. Follow any of them to read the source.
Mechanism boundary: ACTH 1-39 stimulated oligodendroglial progenitor-cell proliferation in rat cultures; this is not dosing evidence.
We found that ACTH 1-39 stimulated proliferation of OPC, and to a lesser extent astroglia (AS) and microglia (MG), in rat glial cultures.
Evidence scope. Animal (rat), in vitro glial cell culture; not human dosing evidence.
Mechanism: subcutaneous ACTH-(1-39) produced dose-responsive increases in cortisol, aldosterone, and 18-hydroxycorticosterone in humans.
Five micrograms of ACTH, sc, was the lowest dose that significantly increased plasma levels of the three steroids.
Evidence scope. Human, healthy adult men (n=9); subcutaneous injection, dose-response pharmacodynamic study.
Claims we could not support
No abstract we checked supports these for this molecule at this route. That is not the same as saying they are false — it marks where the evidence is missing.
Dose/route: 0.25 mg cosyntropin IV/IM. Cosyntropin is ACTH(1-24), not ACTH(1-39). The molecule mismatch prevents using cosyntropin studies for this card.
Primary safety concern: chronic corticosteroid-like immunosuppression/osteoporosis/mood effects. No checked ACTH(1-39) abstract directly supported this safety claim for the displayed regimen.
Plasma
Cortisol peak post-dose
Cortisol response 4-8 hours per dose
subQ ~70%, IM similar
Diagnostic single dose; chronic dosing in Acthar Gel context
Hepatic/renal proteolysis
Storage. Refrigerate. Reconstituted use within 14 days. Acthar Gel per manufacturer label.
FDA-approved formulations: H.P. Acthar Gel for infantile spasms and select autoimmune indications, Cortrosyn (cosyntropin 1-24) for diagnostic adrenal testing. Synthetic ACTH 1-39 as a research chemical is not appropriate for community use. WADA prohibited.
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