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Regulation of adrenocorticotropic hormone secretion: lessons from mice deficient in corticotropin-releasing hormone.
| Content Provider | Semantic Scholar |
|---|---|
| Copyright Year | 2000 |
| Abstract | words of Hans Selye from the 1940s still ring true today. Selye recognized that physical, emotional, and environmental challenges (stressors) elicit a variety of physiological responses and that our ability to respond and adapt to these stressors is critical to our survival. In the 50 years since these initial observations, we have learned a great deal about the complex system that allows us to maintain homeostasis in the resting state and to respond appropriately to stressors, yet much remains to be learned about the regulation of this system. A key component of this stress system is the hypothalamic-pituitary-adrenal (HPA) axis (Figure 1). In response to a stressful stimulus, neural inputs from the central and peripheral nervous system converge on a small nucleus in the hypothalamus (the paraventricular nucleus, or PVN) and signal for increased synthesis and release of corticotropinreleasing hormone (CRH, also known as CRF). This 41–amino acid peptide is released into the hypophyseal portal blood and carried to the anterior pituitary, where it binds to CRH receptors on the corticotropes. As with other Gs protein–coupled membrane receptors, CRH receptors stimulate production of the intracellular second messenger cAMP. Activation of this pathway results in increased production of proopiomelanocortin (POMC) and increased release of adrenocorticotropic hormone (ACTH) and β-endorphin, bioactive proteolytic products of POMC. While CRH is widely regarded as the major hypothalamic releasing factor for ACTH, other hypothalamic compounds such as vasopressin, oxytocin, and norepinephrine can also stimulate ACTH release (at much lower potencies) or potentiate CRH-induced ACTH secretion (reviewed in ref. 1). ACTH is carried via the blood to its target organ, the adrenal cortex, where it stimulates secretion of glucocorticoids (corticosterone in rodents or cortisol in humans). Glucocorticoids then mediate a variety of metabolic effects that help the body to respond to the stressor; for example, they stimulate protein catabolism and gluconeogenesis while inhibiting peripheral glucose uptake. Glucocorticoids also play a critical role in turning off the stress signal to maintain homeostasis in the HPA axis. Elevated glucocorticoid levels reduce the synthesis and release of CRH from the hypothalamus and suppress POMC production and ACTH release in the anterior pituitary. Glucocorticoids also feed back at higher brain centers to modulate the neural inputs to the hypothalamus. Thus, this finely tuned stress system allows us to respond quickly to stressors by increasing CRH, |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.jci.org/articles/view/10002/pdf/render |
| Alternate Webpage(s) | http://dm5migu4zj3pb.cloudfront.net/manuscripts/10000/10002/JCI0010002.pdf |
| PubMed reference number | 10791992v1 |
| Volume Number | 105 |
| Issue Number | 9 |
| Journal | The Journal of clinical investigation |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 8-chloro-cyclic adenosine monophosphate Adrenal Cortex Adrenal Glands Argipressin Axis vertebra CNS disorder Cell Nucleus Convergence (action) Corticosterone Epinephrine Gluconeogenesis Gonadorelin Gonadotropin-Releasing Hormone Receptor Hydrocortisone Hypothalamic structure Inhibition Interphase Cell Norepinephrine Oxytocin POMC gene Peripheral Nervous System Pituitary Hormones, Anterior Receptors, Corticotropin-Releasing Hormone Rodent corticotropin secretion dorsal raphe nucleus glucose uptake negative regulation of phospholipase C-activating G-protein coupled receptor signaling pathway |
| Content Type | Text |
| Resource Type | Article |
