Astressin is an effective non-selective corticotropin-releasing factor (CRF) antagonist, with a low affinity for CRF binding proteins and a high affinity for cloned pituitary receptors (Ki = 2nM) [1]. Astressin can block CRF-induced release of adrenocorticotropic hormone (ACTH) [2]. Astressin can be used as a neuroprotective agent and has an anxiolytic effect [3].
In vitro, treatment with Astressin (200nM; 24h) significantly reduced the secretion of cytokines IL-8 and TNF-α in human HTR-8/SVneo cells co-cultured with corticotropin-releasing hormone (CRH) and lipopolysaccharide (LPS) [4]. Astressin (1, 10, and 100nM; 72h) could increase estrogen (E2) induced proliferation of MCF7 cells in a concentration-dependent manner and reversed the proliferation inhibition of CRH on cells [5].
In vivo, treatment with Astressin (25μg in 4μl saline; intracerebroventricular injection; 30min before and 10min after seizure) effectively protected the neuronal function of rats with excitotoxic epilepsy induced by kainic acid and significantly reduced the damage of hippocampal cells in rats [6]. Treatment with Astressin (5μg/mouse; intraperitoneally; 5 days) could reverse the depigmentation phenotype of CRF overexpressing (OE) alopecia mice, induce pigmentation and hair regrowth, and restored 50–90% hair coverage within 2–4 weeks [7].
References:
[1] Gulyas J, Rivier C, Perrin M, et al. Potent, structurally constrained agonists and competitive antagonists of corticotropin-releasing factor. Proc Natl Acad Sci U S A. 1995;92(23):10575-10579.
[2] Smith S M, Vaughan J M, Donaldson C J, et al. Cocaine-and amphetamine-regulated transcript activates the hypothalamic-pituitary-adrenal axis through a corticotropin-releasing factor receptor-dependent mechanism[J]. Endocrinology, 2004, 145(11): 5202-5209.
[3] Spina M G, Basso A M, Zorrilla E P, et al. Behavioral effects of central administration of the novel CRF antagonist astressin in rats[J]. Neuropsychopharmacology, 2000, 22(3): 230-239.
[4] Wang W, Nan X, Ji P, Dow KE. Corticotropin releasing hormone modulates endotoxin-induced inflammatory cytokine expression in human trophoblast cells. Placenta. 2007;28(10):1032-1038.
[5] Graziani G, Tentori L, Muzi A, et al. Evidence that corticotropin-releasing hormone inhibits cell growth of human breast cancer cells via the activation of CRH-R1 receptor subtype. Mol Cell Endocrinol. 2007;264(1-2):44-49.
[6] Maecker H, Desai A, Dash R, Rivier J, Vale W, Sapolsky R. Astressin, a novel and potent CRF antagonist, is neuroprotective in the hippocampus when administered after a seizure. Brain Res. 1997;744(1):166-170.
[7] Wang L, Million M, Rivier J, et al. CRF receptor antagonist astressin-B reverses and prevents alopecia in CRF over-expressing mice[J]. PLoS One, 2011, 6(2): e16377.
Astressin是一种有效的非选择性的促肾上腺皮质激素释放因子（CRF）拮抗剂，对CRF结合蛋白具有低亲和力，而对克隆的垂体受体具有高亲和力（Ki=2nM） [1]。Astressin可以阻断CRF诱导的促肾上腺皮质激素（ACTH）释放 [2]。Astressin可作为神经保护剂，且具有缓解焦虑作用 [3]。
在体外，Astressin（200nM; 24h）处理显著减少了促肾上腺皮质激素释放激素（CRH）和脂多糖（LPS）共培养的人类HTR-8/SVneo细胞中细胞因子IL-8和TNF-α的分泌 [4]。Astressin（1, 10, and 100nM; 72h）能够以浓度依赖性方式增加雌二醇（E2）诱导的MCF7细胞增殖，并逆转了CRH对细胞的增殖抑制 [5]。
在体内，Astressin（25μg in 4μl saline; 脑室内注射; 癫痫发作前30min和发作后10min）治疗有效保护了Kainic acid诱导的兴奋性毒性癫痫发作大鼠的神经元功能，并显著减少了大鼠海马细胞的损伤 [6]。Astressin（5µg/mouse; i.p.; 5 days）治疗可逆转CRF过度表达（OE）脱毛小鼠的脱发现象，诱导色素沉着和毛发再生，在2–4周恢复了50–90%的毛发覆盖率 [7]。