Additional Target for the Modulation of Sex Hormones and Their Influence on Post Trauma Organ Functions

Previous studies have indicated an interaction between the hypothalamic-pituitary-adrenocortical axis and the hypothalamic-pituitary-gonadal axis are likely the pathway that the brain uses to modulate immune responses in many diseases conditions (Neill, 1970, 1972; Neill and Smith, 1974; Eskandari and Sternberg, 2002; Chaudry et al., 2003; Eskandari et al., 2003). Furthermore, studies have also demonstrated that plasma levels of catecholamines such as norepinephrine, epinephrine, and dopamine are elevated early after the onset of hemorrhage and that sustained levels correlate with irreversibility of shock (Tarnoky and Nagy, 1983; Chaudry et al., 2003). Additionally, studies have shown that administration of the anterior pituitary hormone prolactin enhances immune responses after severe hemorrhage (Zhu et al., 1996; Zellweger et al., 1996a) and decreases mortality from subsequent sepsis (Zhu et al., 1996; Zellweger et al., 1996a, 1996b). Moreover, treatment of animals with the dopamine antagonist metoclo-pramide (MCP), which is known to increase prolactin secretion, had similar beneficial effects on the depressed immune responses after severe hemorrhage (Zellweger et al., 1998; Jarrar et al., 2000d). MCP administration after trauma-hemorrhage also was found to recover the depressed cardiac output and hepatocellular function (Lanza et al., 1987). Furthermore, MCP administration significantly increased circulating levels of prolactin and decreased the plasma levels of the proinflammatory cytokine IL-6. Thus, administration of MCP, which increased prolactin secretion, appears to be a useful adjunct for restoring the depressed cardiac and hepatocellular functions and downregulating inflammatory cytokine release after trauma and hem-orrhagic shock.

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