快樂小藥師 Im pharmacist nichts glücklich

來自：nejm Volume 360:2328-2339 May 28, 2009 Number 22

Cytokines, chemokines, and adipokines derived from immune cells and fat cells and bacterial and viral toxins mediated by toll-like receptors modify pituitary–adrenal hormone synthesis and glucocorticoid tissue sensitivity and the activation of peripheral cortisol metabolism. Similarly, the function of the hypothalamic–pituitary–adrenal axis is influenced by blood flow, endothelial factors, neurotransmitters, and neuropeptides. Furthermore, synthesis of pituitary and adrenal hormones requires a large supply of vitamins, antioxidants, and cholesterol. Impairment and dysregulation of any of these pathways will disrupt the integrity of the hypothalamic–pituitary–adrenal axis and may lead to a disturbed adrenal stress response. An electron micrograph shows the vesicular mitochondria of an adrenocortical cell in a normal mouse and in a mouse with suppressed corticosterone responses due to the administration of dexamethasone (Panels A and B, respectively; uranyl acetate and lead citrate staining). The number and conformational structure of internal mitochondrial membranes correlate with the steroidogenic capacity of an adrenocortical cell. Animal models with a defect in steroid production frequently show alterations in vesicular mitochondria, with reduction and tubular transformation of internal membranes.^19,42Staining of histologic sections of adrenal glands with Sudan black shows the storage of lipid droplets in the adrenal cortex of rats in an unstressed state and 2 hours after stimulation with corticotropin-releasing hormone (Panels C and D, respectively). Since cholesterol constitutes the substrate for steroidogenesis, there is a rapid disappearance of cholesterol-storing liposomes after activation of the hypothalamic–pituitary–adrenal axis (Panel D), illustrating the requirement of an external cholesterol supply for the adrenal gland. CRH denotes corticotropin-releasing hormone, HDL denotes high-density lipoprotein, LDL low-density lipoprotein, and TNF tumor necrosis factor.

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