Description
ACTH 1-39 (corticotropin, adrenocorticotropic hormone) is the complete, 39-amino-acid peptide hormone of the hypothalamic-pituitary-adrenal axis. In the body it is formed as a post-translational cleavage product of the precursor protein proopiomelanocortin (POMC) in the corticotroph cells of the anterior pituitary. This makes ACTH 1-39 the full-length variant, as opposed to the truncated research fragments such as ACTH 1-24 (cosyntropin/tetracosactide).
Mechanistically, ACTH 1-39 binds to the melanocortin-2 receptor (MC2R), a G-protein-coupled receptor located almost exclusively in the adrenal cortex and activated only by ACTH. Activation depends on the accessory membrane protein MRAP1, which stabilizes ACTH at the receptor like a “seat belt”. This triggers a Gs-protein signal, a rise in intracellular cAMP, and the mobilization of cholesterol for steroid synthesis. Studies describe that ACTH increases the number of LDL receptors and drives the rate-limiting step of cortisol synthesis (cholesterol side-chain cleavage to pregnenolone via CYP11A1). The biological activity sits in the first 24 amino acids, while residues 25-39 improve molecular stability and therefore half-life.
On pharmacokinetics: in a human study, alpha-1-39 ACTH (400 mcg intramuscular) was compared against other ACTH preparations. The full-length peptide showed a corticotropic effect lasting up to 12 hours, considerably longer than intravenous ACTH 1-24 (only up to one hour). This extended duration is attributed to the stabilizing C-terminal segment (25-39) that the shorter fragments lack. In studies, ACTH primarily stimulates cortisol from the zona fasciculata, acutely also adrenal androgens such as DHEA, while aldosterone regulation follows mostly other signals (angiotensin II, potassium).
ACTH 1-39 is established in research mainly as an endocrine tool: for investigating adrenal function, HPA-axis dynamics, and steroidogenesis pathways. In the TPD catalog you can get ACTH 1-39 as a single vial in the 5mg size, intended exclusively for laboratory work and endocrinological research applications.
This information is for research and educational purposes only. Not medical advice.
Studies
- ACTH Action on the Adrenals (Angelousi, Margioris, Tsatsanis, Endotext 2020) - comprehensive review of the 39-AA structure, MC2R binding, cAMP signaling, and the controlling steps of cortisol synthesis. PubMed Bookshelf NBK279118.
- Discordance of plasma DHEA-S, DHEA, and cortisol responses with various ACTH regimens (Griffing et al., Metabolism 1985) - human study directly comparing alpha-1-39 ACTH against shorter fragments; the full-length peptide was corticotropic for up to 12 hours.
- Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1 (Luo et al., Cell Research 2023) - cryo-EM structure of the ACTH-bound MC2R-MRAP1-Gs complex; reveals the “seat belt” mechanism of ACTH recognition.
- Development of an adrenocorticotropin-responsive human adrenocortical carcinoma cell line (Parmar, Key, Rainey, J Clin Endocrinol Metab 2008) - in vitro model (HAC15 cell line): ACTH increases the expression of all cortisol-synthesis enzymes via MC2R.
Stack Notes
- With Tesamorelin for endocrine-axis research: while ACTH 1-39 addresses the HPA axis (adrenal cortisol), Tesamorelin as a GHRH analog targets the GH/IGF-1 axis. In research settings examining different pituitary-driven axes in parallel, the two complement each other.
- With Ipamorelin to dissect signaling pathways: Ipamorelin acts via the ghrelin receptor on GH release, ACTH 1-39 via MC2R on the cortisol axis. The combination only makes sense for comparative endocrine model research that looks at different cAMP-coupled receptor systems side by side.
- With MOTS-C in a metabolic research context: MOTS-C addresses mitochondrial and AMPK-mediated metabolic pathways, ACTH 1-39 the glucocorticoid arm of the stress axis. Glucocorticoids and energy metabolism overlap mechanistically, which makes this pairing relevant for studies of the metabolic-endocrine interface.
- No stack with growth or healing peptides without a clear research goal: ACTH 1-39 is a potent modulator of the body’s own cortisol production, not a recovery compound. Unlike BPC-157 or TB-500 (Thymosin B4), which target local tissue pathways, ACTH intervenes systemically in endocrine regulation. A combination only makes sense in specific HPA-axis models, not as a generic “stack” add-on.
