Corticotrophin release

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

Figure 1 A schematic diagram of the endocrine system of fish. TRH = thyrotrophin releasing hormone GnRH = gonadotrophin releasing hormone CRH = corticotrophin releasing hormone TSH = thyroid stimulating hormone GtH = gonadotrophins I and II ...

Among a number of peptides studied it is only the reduction of somatostatin in the temporal, parietal and frontal cortices that correlates with the severity of dementia in AzD, although corticotrophin-releasing factor is lower. Reductions in somatostatin do not generally parallel those of ChAT, its concentration being almost normal in the hippocampus and nucleus basalis, where ChAT levels are lowest and there is no evidence that it is localised in cholinergic neurons. 

Swerdlow N. R., Koob G. F. (1985). Separate neural substrates of the locomotoractivating properties of amphetamine, heroin, caffeine and corticotrophin releasing factor (CRF) in the rat. Pharmacol. Biochem. Behav. 23, 303-7. 

Substance P Cholecystokinin Corticotrophin-releasing factor Melatonin... 

Other tests include the insulin hypoglycemia test, the metyrapone test, and the corticotrophin-releasing hormone stimulation test. 

Clapham DE, Lechleiter JD, Girard S 1993 Intracellular waves observed by confocal microscopy from Xenopus oocytes. Adv Second Messenger Phosphoprot Res 28 161-165 Martin C, Chapman KE, Thornton S, Ashley RH 1999 Changes in the expression of myometrial ryanodine receptor mRNAs during human pregnancy. Biochim Biophys Acta 1451 343—352 McLean M, Smith R 2001 Corticotrophin-releasing hormone and human parturition. Reproduction 121 493-501... 

Neuropeptides are often grouped by their structural similarity or tissue source. Among these are the hypothalamic releasing factors (e.g., corticotrophin-releasing factor [CRF], thyrotropin-releasing hormone), anteior pituitary hormones (e.g., adrenocorticotrophic hormone [ACTFI], follicle-stimulating hormone [FSFI]), and posterior pituitary hormones... 

Several neurotransmitter and receptor changes are observed in Alzheimer s disease (Nordberg 1992). Losses occur in nicotinic receptors, but muscarinic receptors are relatively preserved. Reductions are also seen in serotonin 5-HTl and 5-HT2 receptors. Glutamate NMDA receptors decrease, while kainate receptors increase. j8-adrenergic and dopamine receptors are preserved. Decreases occur in receptors for somatostatin and neuropeptide Y, but corticotrophin-releasing factor receptors increase. Across all receptor subtypes for which there is a loss, the number of receptors decrease but the affinity constant remains unchanged. 

Recent in vitro hybridization studies in the rat have demonstrated that t)rpical antidepressants increase the density of glucocorticoid receptors. Such an effect could increase the negative feedback mechanism and thereby reduce the s)mthesis and release of cortisol. In support of this hypothesis, there is preliminary clinical evidence that metyrapone (and the steroid s)mthesis inhibitor ketoconazole) may have antidepressant effects. Recently several lipophilic antagonists of corticotrophin releasing factor (CRT) type 1 receptor, which appears to be hyperactive in the brain of depressed patients, have been shown to be active in animal models of depression. Clearly this is a potentially important area for antidepressant development. 

Chalmers DT, Lovenberg TW, Grigoriadis DE, Behan DP, De Souza EB (1997) Corticotrophin-releasing factor receptors from molecular biology to drug design. Trends Pharmacol Sci 17 166-172... 

BNST, bed nucleus of the stria terminalis CREB, cyclic AMP response element-binding protein CRH, corticotrophin-releasing hormone CS, conditioned stimuH GABA, y-aminobutyric acid GCC, voltage-gated calcium channels NE, norepinephrine NMDA, iST-methyl-D-aspartate PAG, periaqueductal gray. 

Lightman SL, Young WS 3rd (1988) Corticotrophin-releasing factor, vasopressin and proopiomelanocortin mRNA responses to stress and opiates in the rat. J Physiol 403 511-523 Lolait SJ, O Carroll AM, Mahan LC, Felder CC, Button D, Yoimg III WS, et al (1995) Extra-pituitary expression of the rat Vlb vasopressin receptor gene. Proc Natl Acad Sci USA 92 6783-6787... 

Transcortin acts as a reservoir from which a constant supply of unbound cortisol may be provided to target cells. In addition, when serum albumin levels are low, less circulating cortisol becomes bound, which yields a greater physiological effect. Not only does protein binding control the amount of biologically active cortisol available, but it also reduces the rate at which steroids are cleared from the blood and thus limits steroid suppression of corticotrophin release from the pituitary gland. 

Metyrapone (Metopiwne) produces its primary pharmacological effect by inhibiting ll- -hydroxylase, thereby causing diminished production and release of cortisol. The resulting reduction in the negative feedback of cortisol on the hypothalamus and pituitary causes an increase in corticotrophin release and in the secretion of precursor 11-deoxysteroids. 

Such a medical adrenalectomy is an efficacious treatment for metastatic breast and prostate cancer, since it diminishes the levels of circulating sex hormones. Glucocorticoids are administered concomitantly to suppress enhanced corticotrophin release. Cortisol is preferable to dexamethasone in this situation because aminoglutethimide markedly enhances the hepatic microsomal metabolism of dexamethasone. Hepatic enzyme induction may be responsible for the development of tolerance to the side effects of aminoglutethimide, such as ataxia, lethargy, dizziness, and rashes. 

A) Prompt recovery of the hypothalamic-pituitary-adrenal axis results in restoration of endogenous corticotrophin release. 

---