Wang N, Zhang L, Miles L, Hoover-Plow J
Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Lerner Research Institute, Cleveland, OH 44195, USA.
J Thromb Haemost. 2004 May;2(5):785-96. doi: 10.1111/j.1538-7836.2004.00694.x.
Plasminogen-deficient mice exhibit behavioral differences in response to stress, including a markedly reduced acoustic startle reflex response compared with wild-type (WT) littermates. The acoustic startle reflex activates the hypothalamic-pituitary axis and is modulated by these hormones.
The purpose of this study was to investigate whether plasminogen plays a role in the processing of hormones in the hypothalamic-pituitary axis.
In this study the concentration of plasma, pituitary, and brain hypothalamic-pituitary axis hormones and precursor processing was examined in WT and plasminogen deficient (Plg-/-) mice before and after acoustic startle reflex testing.
Plasma adrenocorticotropic hormone (ACTH), beta-endorphin and alpha-melanocyte stimulating hormone were elevated after acoustic startle reflex testing in both WT and (Plg-/-) mice. However, in the Plg-/- mice, beta-endorphin values were 43, 35, and 45% lower in the plasma, pituitary, and whole brain, respectively, compared with the WT mice. Plasmin readily degraded precursor peptides, the 23-kDa precursor, beta-lipotropin, and ACTH, when presented as purified proteins or as the secretory products of mouse pituitary cells (AtT-20). The precursor peptide, 23 kDa, for beta-endorphin and alpha-melanocyte stimulating hormone was reduced in the pituitaries from the Plg-/- mice, and the mRNA for Plg was found in pituitaries from WT mice. Infusion of beta-endorphin and alpha-melanocyte stimulating hormone into the brain of Plg-/- mice increased acoustic startle reflex.
The results of this study show that plasmin is involved in the processing of hormones derived from the pro-opiomelanocortin precursor in the intermediate pituitary. A deficiency of plasminogen reduces processing of beta-endorphin and alpha-melanocyte stimulating hormone, and interferes with normal brain function.
缺乏纤溶酶原的小鼠在应激反应中表现出行为差异，与野生型（WT）同窝小鼠相比，其听觉惊吓反射反应明显降低。听觉惊吓反射激活下丘脑 - 垂体轴，并受这些激素调节。
本研究旨在调查纤溶酶原是否在下丘脑 - 垂体轴激素加工过程中发挥作用。
在本研究中，对WT和纤溶酶原缺陷（Plg-/-）小鼠在听觉惊吓反射测试前后的血浆、垂体和脑下丘脑 - 垂体轴激素浓度及前体加工情况进行了检测。
WT和Plg-/-小鼠在听觉惊吓反射测试后，血浆促肾上腺皮质激素（ACTH）、β-内啡肽和α-黑素细胞刺激素均升高。然而，与WT小鼠相比，Plg-/-小鼠血浆、垂体和全脑中β-内啡肽值分别低43%、35%和45%。当纤溶酶以纯化蛋白或小鼠垂体细胞（AtT-20）的分泌产物形式存在时，它能轻易降解前体肽、23 kDa前体、β-促脂素和ACTH。Plg-/-小鼠垂体中β-内啡肽和α-黑素细胞刺激素的23 kDa前体肽减少，且在WT小鼠垂体中发现了Plg的mRNA。向Plg-/-小鼠脑内注射β-内啡肽和α-黑素细胞刺激素可增加听觉惊吓反射。
本研究结果表明，纤溶酶参与垂体中间部源自阿片促黑素皮质素原前体的激素加工。纤溶酶原缺乏会减少β-内啡肽和α-黑素细胞刺激素的加工，并干扰正常脑功能。
