Infectious and Tropical Disease Institute, Ohio University, Athens, OH, USA.
Edison Biotechnology Institute, Ohio University, Athens, OH, USA.
Growth Horm IGF Res. 2022 Jun;64:101460. doi: 10.1016/j.ghir.2022.101460. Epub 2022 Apr 15.
Chagas disease (CD) is caused by the protozoan parasite, Trypanosoma cruzi. It affects 7 to 8 million people worldwide and leads to approximately 50,000 deaths per year. In vitro and in vivo studies had demonstrated that Trypanosoma cruziinfection causes an imbalance in the hypothalamic-pituitary-adrenal (HPA) axis that is accompanied by a progressive decrease in growth hormone (GH) and prolactin (PRL) production. In humans, inactivating mutations in the GH receptor gene cause Laron Syndrome (LS), an autosomal recessive disorder. Affected subjects are short, have increased adiposity, decreased insulin-like growth factor-I (IGFI), increased serum GH levels, are highly resistant to diabetes and cancer, and display slow cognitive decline. In addition, CD incidence in these individuals is diminished despite living in highly endemic areas. Consequently, we decided to investigate the in vitro effect of GH/IGF-I on T. cruzi infection.
We first treated the parasite and/or host cells with different peptide hormones including GH, IGFI, and PRL. Then, we treated cells using different combinations of GH/IGF-I attempting to mimic the GH/IGF-I serum levels observed in LS subjects.
We found that exogenous GH confers protection against T. cruzi infection. Moreover, this effect is mediated by GH and not IGFI. The combination of relatively high GH (50 ng/ml) and low IGF-I (20 ng/ml), mimicking the hormonal pattern seen in LS individuals, consistently decreased T. cruzi infection in vitro.
The combination of relatively high GH and low IGF-I serum levels in LS individuals may be an underlying condition providing partial protection against T. cruzi infection.
恰加斯病（CD）是由原生动物寄生虫克氏锥虫引起的。它影响全球 700 至 800 万人，并导致每年约 5 万人死亡。体外和体内研究表明，克氏锥虫感染会导致下丘脑-垂体-肾上腺（HPA）轴失衡，伴随生长激素（GH）和催乳素（PRL）产生的逐渐减少。在人类中，GH 受体基因突变会导致拉隆综合征（LS），这是一种常染色体隐性遗传病。受影响的个体身材矮小，脂肪过多，胰岛素样生长因子-I（IGFI）减少，血清 GH 水平升高，对糖尿病和癌症高度抵抗，认知能力下降缓慢。此外，尽管生活在高度流行地区，这些个体的 CD 发病率降低。因此，我们决定研究 GH/IGF-I 对 T. cruzi 感染的体外影响。
我们首先用包括 GH、IGFI 和 PRL 在内的不同肽激素处理寄生虫和/或宿主细胞。然后，我们用 GH/IGF-I 的不同组合处理细胞，试图模拟 LS 患者中观察到的 GH/IGF-I 血清水平。
我们发现外源性 GH 可提供针对 T. cruzi 感染的保护。此外，这种作用是由 GH 介导的，而不是 IGFI。相对高 GH（50ng/ml）和低 IGFI（20ng/ml）的组合，模拟 LS 个体中观察到的激素模式，一致降低了体外 T. cruzi 感染。
LS 个体中相对高 GH 和低 IGFI 血清水平的组合可能是提供针对 T. cruzi 感染的部分保护的潜在条件。
