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A chilled-out knockout

Nature Genetics volume 19, pages 108–109 (1998)Cite this article

Stress is the most common disorder of our century — most of us know too well what it means to be 'stressed out'. The word 'stress' is often used to mean anxiety regarding conditions that may be physical, environmental or emotional. In biological and molecular terms, however, stress is a critical physiological response of the body to threatening situations; it is a response that results in enhanced vigilance and allows our bodies to react to a striking number of diverse cues.

The best-characterized response to stress affects the hypothalamus-pituitary-adrenal (HPA) axis (see figure). Signals originating in the central or peripheral nervous system are conveyed to centres located in the hypothalamus. A molecular cascade of events is then triggered by one molecule: the corticotropin-releasing hormone (CRH; also known as CRF). CRH is a peptide, most of which is synthesized in small nuclei of the hypothalamus, whereupon it is released in the portal-vein system which delivers it to the hypophysis or pituitary gland. Here, CRH interacts with membrane receptors present on the membrane of two pituitary cell types: the corticotrophs and the melanotrophs. Interaction of CRH with the cognate receptor (CRHR) evokes the production of second-messenger cyclic AMP in the target cells. Stimulation of pituitary corticotrophs by CRH results in the production of the adrenocorticotropic hormone (ACTH) and the primary target tissue of ACTH is the cortex of the adrenal gland, from which it elicits the release of glucocorticoids (cortisol in humans and corticosterone in rodents) through interaction with ACTH receptors. Glucocorticoids in turn signal to the pituitary and the brain to turn off the response to stressful stimuli. In addition, a direct effect of CRH on other regions of the brain has also been described, indicating that this peptide might act not only as a neurohormone but also as a neuromodulator1.

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  1. Institut de Génetique et de Biologie Moléculaire et Cellulaire CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, CU de Strasbourg, France

    Emiliana Borrelli

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  1. Emiliana Borrelli
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Borrelli, E. A chilled-out knockout. Nat Genet 19, 108–109 (1998). https://doi.org/10.1038/452

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