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Plasminogen regulates pro‐opiomelanocortin processing

Journal of Thrombosis and Haemostasis, ISSN: 1538-7836, Vol: 2, Issue: 5, Page: 785-796
2004
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Article Description

Background 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. Objectives The purpose of this study was to investigate whether plasminogen plays a role in the processing of hormones in the hypothalamic–pituitary axis. Methods 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. Results Plasma adrenocorticotropic hormone (ACTH), β‐endorphin and α‐melanocyte stimulating hormone were elevated after acoustic startle reflex testing in both WT and (Plg–/–) mice. However, in the Plg–/– mice, β‐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, β‐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 β‐endorphin and α‐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 β‐endorphin and α‐melanocyte stimulating hormone into the brain of Plg–/– mice increased acoustic startle reflex. Conclusions 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 β‐endorphin and α‐melanocyte stimulating hormone, and interferes with normal brain function.

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