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Plasminogen regulates pro-opiomelanocortin processing.
- Source :
-
Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2004 May; Vol. 2 (5), pp. 785-96. - Publication Year :
- 2004
-
Abstract
- 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.<br />Objectives: The purpose of this study was to investigate whether plasminogen plays a role in the processing of hormones in the hypothalamic-pituitary axis.<br />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.<br />Results: 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.<br />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 beta-endorphin and alpha-melanocyte stimulating hormone, and interferes with normal brain function.
- Subjects :
- Adrenocorticotropic Hormone blood
Adrenocorticotropic Hormone metabolism
Animals
Fibrinolysin physiology
Hormones blood
Hormones metabolism
Hypothalamo-Hypophyseal System metabolism
Melanocyte-Stimulating Hormones blood
Melanocyte-Stimulating Hormones metabolism
Mice
Mice, Knockout
Plasminogen deficiency
Plasminogen genetics
RNA, Messenger analysis
Reflex, Acoustic
beta-Endorphin blood
beta-Endorphin metabolism
Plasminogen physiology
Pro-Opiomelanocortin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7933
- Volume :
- 2
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and haemostasis : JTH
- Publication Type :
- Academic Journal
- Accession number :
- 15099286
- Full Text :
- https://doi.org/10.1111/j.1538-7836.2004.00694.x