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      Testosterone cannot activate an adult-like stress response in prepubertal male rats.

      Neuroendocrinology
      Adaptation, Physiological, Adrenocorticotropic Hormone, blood, Age Factors, Analysis of Variance, Animals, Corticosterone, Hypothalamo-Hypophyseal System, physiology, Male, Pituitary-Adrenal System, Rats, Rats, Sprague-Dawley, Sexual Maturation, Stress, Physiological, Stress, Psychological, Testosterone

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          Abstract

          The pubertal maturation of the hypothalamic-pituitary-adrenal (HPA) axis has received relatively little experimental attention. The present set of experiments sought to extend our understanding of the pubertal stress response by measuring corticotropin (ACTH), corticosterone, and testosterone levels in prepubertal and adult male rats exposed to a single 30-min session of restraint stress. We show that ACTH and corticosterone levels in prepubertal males take significantly longer to return to baseline after termination of the stressor compared to adults. These data indicate that prepubertal males demonstrate a more prolonged stress response compared to adults after a single acute stressor with both psychogenic and neurogenic components. As testosterone has been shown to reduce the stress response in adulthood, we next investigated whether the relatively low levels of circulating testosterone in prepubertal males mediated their protracted stress response. Data collected from additional experiments revealed that prepubertal males treated with adult-like physiological levels of testosterone still exhibited an extended stress response compared to similarly treated adults. These results indicate that the stress response demonstrated by adult males cannot be mimicked or activated in prepubertal males by mere supplementation of testosterone. Thus, we conclude that the HPA neuroendocrine axis is further shaped during pubertal development to allow for the emergence of a more tightly regulated stress response in adulthood. Copyright 2004 S. Karger AG, Basel

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          Most cited references9

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          Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis.

          Integration of the hypothalamo-pituitary-adrenal stress response occurs by way of interactions between stress-sensitive brain circuitry and neuroendocrine neurons of the hypothalamic paraventricular nucleus (PVN). Stressors involving an immediate physiologic threat ('systemic' stressors) are relayed directly to the PVN, probably via brainstem catecholaminergic projections. By contrast, stressors requiring interpretation by higher brain structures ('processive' stressors) appear to be channeled through limbic forebrain circuits. Forebrain limbic sites connect with the PVN via interactions with GABA-containing neurons in the bed nucleus of the stria terminalis, preoptic area and hypothalamus. Thus, final elaboration of processive stress responses is likely to involve modulation of PVN GABAergic tone. The functional and neuroanatomical data obtained suggest that disease processes involving inappropriate stress control involve dysfunction of processive stress pathways.
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            Functional cross-talk between the hypothalamic-pituitary-gonadal and -adrenal axes.

            V Viau (2002)
            Under normal conditions, the adrenal glucocorticoids, the endproduct of the hypothalamic-pituitary-adrenal (HPA) axis, provide a frontline of defence against threats to homeostasis (i.e. stress). On the other hand, chronic HPA drive and glucocorticoid hypersecretion have been implicated in the pathogenesis of several forms of systemic, neurodegenerative and affective disorders. The HPA axis is subject to gonadal influence, indicated by sex differences in basal and stress HPA function and neuropathologies associated with HPA dysfunction. Functional cross-talk between the gonadal and adrenal axes is due in large part to the interactive effects of sex steroids and glucocorticoids, explaining perhaps why several disease states linked to stress are sex-dependent. Realizing the interactive nature by which the hypothalamic-pituitary-gonadal and HPA systems operate, however, has made it difficult to model how these hormones act in the brain. Manipulation of one endocrine system is not without effects on the other. Simultaneous manipulation and assessment of both endocrine systems can overcome this problem. This dual approach in the male rat reveals that testosterone can act and interact on different aspects of basal and stress HPA function. Basal adrenocorticotropic hormone (ACTH) release is regulated by testosterone-dependent effects on arginine vasopressin synthesis, and corticosterone-dependent effects on corticotropin-releasing hormone (CRH) synthesis in the paraventricular nucleus (PVN) of the hypothalamus. In contrast, testosterone and corticosterone interact on stress-induced ACTH release and drive to the PVN motor neurones. Candidate structures mediating this interaction include several testosterone-sensitive afferents to the HPA axis, including the medial preoptic area, central and medial amygdala and bed nuclei of the stria terminalis. All of these relay homeostatic information and integrate reproductive and social behaviour. Because these modalities are affected by stress in humans, a dual systems approach holds great promise in establishing further links between the neuroendocrinology of stress and the central bases of sex-dependent disorders, including psychiatric, cardiovascular and metabolic disease.
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              The role of stress in drug self-administration.

              Environmental experiences have an important effect on the sensitivity of an individual to drugs of abuse. Studies of drug self-administration in laboratory animals have shown that both physical and psychological stressors facilitate the acquisition of drug self-administration, probably by increasing the reinforcing efficacy of drugs of abuse. Stressors also facilitate the reinstatement of drug taking even after prolonged periods of withdrawal. The adrenal hormones, glucocorticoids, which increase the sensitivity of mesencephalic dopaminergic neurones to drugs, seem to be one of the biological substrates of the effects of stress on the propensity to develop drug intake. In this review, Pier Vincenzo Piazza and Michel Le Moal discuss theories of drug abuse, the influence of different stressful experiences on drug self-administration and their possible mechanisms of action.
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