59
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      ENDOCRINOLOGY OF THE STRESS RESPONSE

      1 , 1 , 1
      Annual Review of Physiology
      Annual Reviews

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The stress response is subserved by the stress system, which is located both in the central nervous system and the periphery. The principal effectors of the stress system include corticotropin-releasing hormone (CRH); arginine vasopressin; the proopiomelanocortin-derived peptides alpha-melanocyte-stimulating hormone and beta-endorphin, the glucocorticoids; and the catecholamines norepinephrine and epinephrine. Appropriate responsiveness of the stress system to stressors is a crucial prerequisite for a sense of well-being, adequate performance of tasks, and positive social interactions. By contrast, inappropriate responsiveness of the stress system may impair growth and development and may account for a number of endocrine, metabolic, autoimmune, and psychiatric disorders. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors, and the timing of the stressful events, given that prenatal life, infancy, childhood, and adolescence are critical periods characterized by increased vulnerability to stressors.

          Related collections

          Most cited references84

          • Record: found
          • Abstract: found
          • Article: not found

          The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress.

          In the studies reported here we have examined the role of the medial prefrontal cortex (MpFC) in regulating hypothalamic-pituitary-adrenal (HPA) activity under basal and stressful conditions. In preliminary studies we characterized corticosteroid receptor binding in the rat MpFC. The results revealed high-affinity (Kd approximately 1 nM) binding with a moderate capacity (42.9 +/- 3 fmol/mg) for 3H-aldosterone (with a 50-fold excess of cold RU28362; mineralocorticoid receptor) and high-affinity (Kd approximately 0.5-1.0 nM) binding with higher capacity (183.2 +/- 22 fmol/mg) for 3H-RU 28362 (glucocorticoid receptor). Lesions of the MpFC (cingulate gyrus) significantly increased plasma levels of both adrenocorticotropin (ACTH) and corticosterone (CORT) in response to a 20 min restraint stress. The same lesions had no effect on hormone levels following a 2.5 min exposure to ether. Implants of crystalline CORT into the same region of the MpFC produced a significant decrease in plasma levels of both ACTH and CORT with restraint stress, but again, there was no effect with ether stress. Neither MpFC lesions nor CORT implants had any consistent effect on A.M. or P.M. levels of plasma ACTH or CORT. Manipulations of MpFC function were not associated with changes in the clearance rate for CORT or in corticosteroid receptor densities in the pituitary, hypothalamus, hippocampus, or amygdala. Taken together, these findings suggest that MpFC is a target site for the negative-feedback effects of glucocorticoids on stress-induced HPA activity, and that this effect is dependent upon the nature of the stress.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes.

            The stress system coordinates the adaptive response of the organism to real or perceived stressors. The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine/ autonomic (LC/NE) systems and their peripheral effectors, the hypothalamic-pituitary-adrenal (HPA) axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. Thus, CRH and the LC/NE system stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the amygdala, which are responsible for the generation of fear. Hypothalamic CRH plays an important role in inhibiting gonadotropin-releasing hormone secretion during stress, while via somatostatin it also inhibits growth hormone, thyrotropin-releasing hormone and thyrotropin secretion, suppressing thus reproduction, growth and thyroid function. Glucocorticoids directly inhibit pituitary gonadotropin, growth hormone and thyrotropin secretion and make the target tissues of sex steroids and growth factors resistant to these substances. In addition, glucocorticoids stimulate hepatic gluconeogenesis, and inhibit or potentiate insulin actions on skeletal muscle and adipose tissue respectively, ultimately promoting visceral adiposity and the metabolic syndrome. Glucocorticoids also have direct effects on the bone, inhibiting osteoblastic activity and causing osteoporosis. Obese subjects with psychiatric manifestations ranging from those of melancholic depression to anxiety with perception of 'uncontrollable' stress, frequently have mild hypercortisolism, while carefully screened obese subjects with no such manifestations are eucortisolemic. The former may have stress-induced glucocorticoid-mediated visceral obesity and metabolic syndrome manifestations, which in the extreme may be called a pseudo-Cushing state that needs to be differentiated from frank Cushing syndrome. Stress-induced hypercortisolism and visceral obesity and their cardiovascular and other sequelae increase the all-cause mortality risk of affected subjects by 2-3-fold and curtail their life expectancy by several years.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Corticosteroid inhibition of ACTH secretion.

              Corticosteroid feedback inhibits the brain-hypothalamo-pituitary units of the adrenocortical system. Naturally occurring corticosteroids may have their primary actions in vivo at brain and hypothalamic sites of feedback, whereas synthetic glucocorticoids that do not bind to transcortin may act primarily on corticotropes and regions of brain outside the blood-brain barrier. There appear to be three major time frames of corticosteroid action: fast, intermediate and slow. These time frames probably are the consequence of three separate mechanisms of corticosteroid action at feedback-sensitive sites. The rapidity of occurrence of fast feedback is not compatible with a nuclear site of corticosteroid action, and protein synthesis is not required. The action of CRF on ACTH release may be inhibited by a rapid effect of corticosteroids at the cell membrane. Since stimulated, but not basal, ACTH and CRF release are inhibited in vitro, the corticosteroids may inhibit some event in stimulus-secretion coupling (e.g., cAMP production). Intermediate feedback also decreases ACTH release in response to stimulation of the corticotrope, but does not affect ACTH synthesis; CRF synthesis and release both appear to be affected by the intermediate corticosteroid action. The mechanism of intermediate feedback requires the presence of a protein whose synthesis is corticosteroid-dependent; however, the role of this protein is unknown. Intermediate feedback, like fast feedback, apparently does not involve inhibition of total ACTH stores or the releasable pool of ACTH since basal secretion of ACTH is also not inhibited in vitro within this time domain. On the other hand, slow feedback apparently involves the classical genomic steroid mechanism of action; slow feedback reduces pituitary ACTH content by decreasing levels of mRNA encoding for POMC, the ACTH precursor molecule. Slow feedback, therefore, inhibits basal as well as stimulus induced ACTH secretion. Corticosteroid-induced inhibition of basal ACTH secretion has been shown to occur within 2 h in vivo but not in vitro. The time course and sensitivity of this feedback effect is different than that demonstrated for stimulus induced secretion. This difference suggests that basal secretion is activated by different pathways to (CRF and) ACTH secretion. There is some evidence that suggests that whereas comparator elements are not reset during stress, a comparator element is reset during the course of the circadian rhythm so that different basal levels of steroid are achieved.(ABSTRACT TRUNCATED AT 400 WORDS)
                Bookmark

                Author and article information

                Journal
                Annual Review of Physiology
                Annu. Rev. Physiol.
                Annual Reviews
                0066-4278
                1545-1585
                March 17 2005
                March 17 2005
                : 67
                : 1
                : 259-284
                Affiliations
                [1 ]Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, and Hellenic National Diabetes Center, Athens, 10675, Greece; email: ;
                Article
                10.1146/annurev.physiol.67.040403.120816
                15709959
                e84d58ef-6137-464e-a6bf-d274432213a6
                © 2005
                History

                Comments

                Comment on this article