Glucocorticoids brain

Steroid Hormones and Neurosteroids. Steroids (qv) can affect neuroendocrine function, stress responses, and behavioral sexual dimorphism (78,79) (see Steroids). Mineralocorticoid, glucocorticoid, androgen, estrogen, and progesterone receptors are localized in the brain and spinal cord. In addition to genomic actions, the neurosteroid can act more acutely to modulate the actions of other receptors or ion channels (80). Pregnenolone [145-13-17, ( ) dehydroepiandosterone [53-43-0] C H2 02 (319) are excitatory neurosteroids found in rat brain, independent of adrenal... 

Although MR also binds glucocorticoids, its main ligand in classical mineralocorticoid target tissues such as kidney and colon is aldosterone ( d 1.3 nM). This can be granted to the ability of 11 (3-hydioxysteroid dehydrogenase type II (11 (3-HSD II) to convert active cortisol into its inactive metabolite cortisone in these tissues. Since aldosterone is no substrate for this enzyme it can readily bind to MR, leading to exclusive occupation of the receptor by aldosterone. In contrast, no such mechanism exists in brain and presumably... 

Gravel, A. and Vijayan, M.M. (2006). Sahcylate disrupts interrenal steroidogenesis and brain glucocorticoid receptor expression in rainbow trout. Toxicology Science 93, 41-49. 

Chao, H., Choo, P. and McEwen, B. Glucocorticoid and mineralocorticoid receptor mRNA expression in rat brain. Neuroendocrinology 50 365-371,1989. 

Yamagata, K., Andreasson, K. I., Kaufmann, W. E., Barnes, C. A. and Worley, P. F. Expression of a mitogen-inducible cyclooxygenase in brain neurons regulation by synaptic activity and glucocorticoids. Neuron 11 371-386,1993. 

Glucocorticoid. Adrenal steroid receptors have been subdivided into two categories, one of which is the classical glucocorticoid receptor [7,19]. This receptor, cloned from human and rat sources, consists of a steroid- and DNA-binding subunit of 95 kDa [7, 19]. Such receptors, which have dissociation constants of 4-5 nM for glucocorticoids, are widely distributed across brain regions and are found in neurons and glial cells [7,19]. 

The potential hyperactivation of the HPA axis in mood disorders has been revisited in recent years, in large part due to the growing recognition of the specific brain areas in which atrophy (loss), a neuroplastic event, may be present in many patients. To what extent these findings of atrophy represent the sequelae of the biochemical changes (for example, in glucocorticoid levels) accompanying repeated affective episodes, remains to be fully elucidated. 

Matthews, S.G., Dynamic changes in glucocorticoid andmineralocorticoidreceptormRNA in the developing guinea pig brain, Dev. BrainRes., 107, 123,1998. 

McCormick, C.M. et al., Sex-specific effects of prenatal stress on hypothalamic-pituitary-adrenal responses to stress and brain glucocorticoid receptor density in adult rats, Dev. BrainRes., 84, 55, 1995. 

Eldridge JC, Landfield PW. (1990). Cannabinoid interactions with glucocorticoid receptors in rat hippocampus. Brain Res. 534(1-2) 135-41. 

Luo L-G, Jackson IMD. 1999. Advantage of double labeled in situ hybridization for detecting the effects of glucocorticoids on the mRNAs of protooncogenes and neural peptides TRH in cultured hypothalamic neurons. Brain Res Prot 4 201-208. 

It has been hypothesized that depression could arise from a pathological enhancement of 5-HT2 receptor function. This view would concur with the observations that the functional activity of 5-HT2 receptors on the platelet membrane is enhanced in depression and the increase in the density of 5-HT2 receptors in the frontal cortex of brains from suicide victims. It is possible that enhanced 5-HT2 receptor function is associated primarily with anxiety, a common feature of depression, and that the increased activity of the 5-HT2 receptors results in an attenuation of the functioning of S-HT receptors thereby resulting in the symptoms of depression. Whether this change in the activity of S-HT receptors is due to direct effects of the altered 5-HT2 receptor function is uncertain. There is evidence that hypercortisolaemia, which is a characteristic feature of depression, reduces the activity of these receptors probably through central glucocorticoid type 2 receptors. Clearly further research is needed to determine the precise interaction between the 5-HT2 and 5-HTi receptor types. 

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. 

Table 7.7. Role of glucocorticoids in modulating brain amines in depression...

Glucocorticoid receptors occur on catecholamine and 5-EIT cell bodies in the brain. 

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