The next two axes, at the bottom of Figure 10-3, differ from the others, involving not central coordination but distributive production and regulation, with the brain as a primary target organ. The (5) adiposal axis (bottom center) comprises white adipocytes in fat depots throughout the periphery that produce leptin, which acts in the brain and periphery with metabolic, reproductive, affective, and even hemopoeitic effects (Harris, 2000; Mantzoros, 1999; Wauters et al., 2000). This axis is significant for the present discussion because it clearly ties energetic status (not just energy stores but the balance of intake and expenditure) not only to prioritization of energy use (reproduction, metabolism) but also to mood and behavior (Baile et al., 2000; Havel, 2001; Maes, 1999; Mantzoros et al., 2001; Trayhurn and Rayner, 1996). Gonadal steroids also influence adipocyte activity and distribution (Anderson et al., 2001). Multiple neuropeptides, chiefly neuropeptide Y (NPY), proopiomelanocortin (POMC), and agouti-related peptide, mediate the actions of leptin on thermogenesis and energy metabolism and its hypothalamically mediated impact on other axes, including the gonadal. Indeed, one of the earliest observed stigmata of leptin-deficient mice was infertility (Caprio et al., 2001; Caro et al., 1996). But dense neuroendocrine pathways also tie leptin and a closely allied hormone, insulin, to motivation, affect, and behavior, which may be represented by hunger, irritability, and food intake, respectively (Mantzoros and Moschos, 1998; Schwartz et al., 1997).

The last axis, (6) the immunologic (bottom left), is stunningly complex and highly distributive. In addition to its primary place in the maintenance of physical health and integrity, the immune system strongly affects mood and behavior via cytokines released in the course of its normal pathogen-defense and repair actions (Anisman et al., 1999; Owen et al., 2001). This effect is most vividly manifested in sickness behavior—the listlessness, anorexia, social withdrawal, and cognitive blunting that accompany illness or injury (Dantzer, 2001; Hart, 1988; Yirmiya et al., 2000). Cytokine activation also suppresses sexual behavior, although animal models suggest that this effect is much more pronounced in females than males (Avitsur and Yirmiya, 1999). In addition to their potent psychobehavioral effects, cytokines trigger shunting of energy away from growth or reproduction via activation of the HPA axis and direct central effects on the HPG and somatotropic axes, suppression of thyroid activity, and peripheral actions on target organs (Rasmussen, 2000; Rivest and Rivier, 1995; von Laue and Ross, 2000).

This brief survey of endocrine architecture reveals that life history parameters have demonstrable physiological bases and furthermore raises several points about neuro-endocrine function. First, neuro-endocrine activity can be seen as clearly aimed at allocating resources among the domains of growth, reproduction, and maintenance. Neuro-endocrine path-



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