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ClinicalFull-length adrenal hormone with broad receptor activity

ACTH 1-39

Also indexed as Adrenocorticotropic Hormone 1-39, Corticotropin, ACTH

ACTH 1-39 is the full-length, biologically active form of adrenocorticotropic hormone, a 39-amino acid peptide naturally secreted by the anterior pituitary gland. It primarily stimulates the adrenal cortex to produce cortisol, aldosterone, and adrenal androgens. Beyond adrenal signaling, ACTH 1-39 exerts direct effects on the brain, immune system, and peripheral tissues via melanocortin receptors.

Overview

Following IM or subQ administration, ACTH 1-39 has a very short plasma half-life (~10–15 minutes) due to rapid proteolytic degradation. Despite this, downstream cortisol elevations persist for 2–4 hours. Volume of distribution is low (~0.1 L/kg), suggesting limited tissue penetration beyond receptor-dense target organs. The full 1-39 sequence offers marginally improved receptor engagement at MC1R, MC3R, and MC4R compared to the 1-24 fragment, potentially amplifying extra-adrenal melanocortin effects. Chronic administration leads to adrenocortical hypertrophy and increased zona fasciculata and reticularis mass.

Proposed mechanism

ACTH 1-39 binds primarily to the melanocortin-2 receptor (MC2R) on adrenal cortex cells, activating adenylyl cyclase via Gs-protein coupling, elevating cAMP, and triggering the steroidogenic cascade that converts cholesterol to cortisol and other glucocorticoids. It also binds MC1R, MC3R, MC4R, and MC5R on non-adrenal tissues, mediating anti-inflammatory, neuroprotective, and lipolytic effects independent of cortisol. The N-terminal 1-24 fragment contains the receptor-binding core, while residues 25-39 extend bioavailability and modulate receptor selectivity.

What the evidence supports

Randomised controlled trial data in humans exists and supports use in specific contexts.

Graded Clinical

Findings supported by randomised, controlled trials in humans, with pre-registered endpoints and published results.

Key citations

Representative primary sources, including results that did not favour the compound.

  1. [1]

    Structure and function of adrenocorticotropin

    · Endocrine Reviews 24(3):374-402 · 2003

  2. [2]

    Melanocortin receptors: their ligands, physiological functions and the effects of their deficiency

    · Pharmacological Reviews 58(2):261-284 · 2006

  3. [3]

    ACTH and the adrenocortical axis: basic science and clinical aspects

    · Clinical Endocrinology 84(1):1-12 · 2016

  4. [4]

    Extra-adrenal effects of ACTH on immune and nervous system function

    · Annals of the New York Academy of Sciences 1220:139-148 · 2011

Citation records in this build are illustrative placeholders for the design.

Reference information for research purposes. Not medical advice, and not a recommendation to use any compound. Many entries describe substances that are not approved for human use.

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