Adrenocorticotropic Hormone (ACTH) (1-39) is a potent melanocortin 2 receptor (MC2R) agonist produced by the anterior pituitary gland. As a key component of the hypothalamic-pituitary-adrenal (HPA) axis, ACTH (1-39) binds to MC2R on the surface of adrenal cells, activating the cAMP-PKA signaling pathway and thereby promoting the conversion of cholesterol to cortisol[1,2]. ACTH (1-39) is commonly used for the diagnosis of adrenal function and in the treatment and research of diseases such as multiple sclerosis relapse[3,4].
In vitro, pretreatment of neurons with ACTH (1-39) (200, 400nM) for 30min, followed by co-incubation with 25μM Quinolinic acid or Kynurenic acid for 24h, significantly attenuated Quinolinic acid-induced neuronal death, but showed no protective effect against Kynurenic acid-induced cell death[5]. Pretreatment of normal human epidermal melanocytes with ACTH (1-39) (100nM) for 24h significantly stimulated the production of cortisol and corticosterone[6]. Treatment of adrenal cells isolated from rats of different postnatal ages with ACTH (1-39) (1ng/mL) for 2h significantly enhanced corticosterone production, and this effect increased with developmental age[7].
In vivo, ACTH (1-39) (5μg), administered intra-articularly in a monosodium urate (MSU) crystal-induced recurrent arthritis model in rats (given concurrently with the second MSU injection at 72h after the first injection), significantly suppressed neutrophil infiltration, joint swelling, and arthritis scores at 96h[8]. Additionally, ACTH (1-39) (0.3mg/kg/day), delivered via continuous subcutaneous infusion using an osmotic minipump and co-administered with DEX in mice for 4 days, prevented the adrenal weight loss induced by DEX alone and completely blocked apoptosis of adrenocortical cells[9].
References:
[1] GALLO-PAYET N. 60 years of POMC: adrenal and extra-adrenal functions of ACTH[J]. Journal of molecular endocrinology, 2016, 56(4): T135-T156.
[2] HASENMAJER V, BONAVENTURA I, MINNETTI M, et al. Non-canonical effects of ACTH: insights into adrenal insufficiency[J]. Frontiers in endocrinology, 2021, 12: 701263.
[3] OELKERS W, DIEDERICHS S, BÄHR V. Diagnosis and therapy surveillance in Addison's disease: rapid adrenocorticotropin (ACTH) test and measurement of plasma ACTH, renin activity, and aldosterone[J]. The Journal of Clinical Endocrinology & Metabolism, 1992, 75(1): 259-264.
[4] BENJAMINS J A, NEDELKOSKA L, LISAK R P. Melanocortin receptor subtypes are expressed on cells in the oligodendroglial lineage and signal ACTH protection[J]. Journal of neuroscience research, 2018, 96(3): 427-435.
[5] LISAK R P, NEDELKOSKA L, BEALMEAR B, et al. Melanocortin receptor agonist ACTH 1-39 protects rat forebrain neurons from apoptotic, excitotoxic and inflammation-related damage[J]. Experimental Neurology, 2015, 273: 161-167.
[6] SLOMINSKI A, ZBYTEK B, SZCZESNIEWSKI A, et al. CRH stimulation of corticosteroids production in melanocytes is mediated by ACTH[J]. American Journal of Physiology-Endocrinology and Metabolism, 2005, 288(4): E701-E706.
[7] LEE J J, EISENBERG P, PAPADOPOULOS V, et al. Reversible changes in adrenocorticotropin (ACTH)-induced adrenocortical steroidogenesis and expression of the peripheral-type benzodiazepine receptor during the ACTH-insensitive period in young rats[J]. Endocrinology, 2004, 145(5): 2165-2173.
[8] GETTING S J, CHRISTIAN H C, FLOWER R J, et al. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis[J]. Arthritis & Rheumatism, 2002, 46(10): 2765-2775.
[9] THOMAS M, KERAMIDAS M, MONCHAUX E, et al. Dual hormonal regulation of endocrine tissue mass and vasculature by adrenocorticotropin in the adrenal cortex[J]. Endocrinology, 2004, 145(9): 4320-4329.
Adrenocorticotropic Hormone (ACTH) (1-39)是一种由垂体前叶产生的有效的黑皮质素2受体（MC2R）激动剂。ACTH (1-39)是下丘脑-垂体-肾上腺（HPA）轴的关键部分，通过与肾上腺细胞表面的MC2R结合，激活cAMP-PKA信号通路，进而促进胆固醇转化为皮质醇[1,2]。ACTH (1-39)通常用于肾上腺功能的诊断及多发性硬化症复发等疾病的治疗和研究[3,4]。
在体外，ACTH (1-39)（200, 400nM）预处理神经元30min，再加入25μM Quinolinic acid或Kynurenic acid处理24h，显著减轻了Quinolinic引起的神经元死亡，但对Kynurenic诱导的细胞死亡无保护作用[5]。ACTH (1-39)（100nM）预处理正常人表皮黑素细胞24h，可显著刺激皮质醇和皮质酮的生成[6]。ACTH (1-39)（1ng/mL）处理从不同日龄大鼠分离的肾上腺细胞2h，显著增强了皮质酮的生成，且该效应随发育年龄增长而增强[7]。
在体内，ACTH (1-39)（5μg）通过关节内给药处理单钠尿酸盐（MSU）晶体诱导的复发性大鼠关节炎模型（于首次注射72h后，第二次注射MSU时同时给药），能显著抑制96h时段的中性粒细胞浸润、关节肿胀和关节炎评分[8]。ACTH (1-39)（0.3mg/kg/day）通过皮下植入的微型泵持续输注与DEX共同处理小鼠4天，可防止由DEX单独处理引起的肾上腺重量减轻，并完全阻断了肾上腺皮质细胞的凋亡[9]。