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2_test

{"project":"2_test","denotations":[{"id":"24103554-16412623-70233225","span":{"begin":1238,"end":1241},"obj":"16412623"},{"id":"24103554-18339373-70233226","span":{"begin":1549,"end":1552},"obj":"18339373"},{"id":"24103554-2070776-70233227","span":{"begin":1676,"end":1679},"obj":"2070776"},{"id":"24103554-17290797-70233228","span":{"begin":1680,"end":1683},"obj":"17290797"},{"id":"24103554-7715646-70233229","span":{"begin":1920,"end":1923},"obj":"7715646"},{"id":"24103554-7715646-70233230","span":{"begin":2089,"end":2092},"obj":"7715646"},{"id":"24103554-19837912-70233231","span":{"begin":2261,"end":2264},"obj":"19837912"},{"id":"24103554-17208436-70233232","span":{"begin":2286,"end":2289},"obj":"17208436"},{"id":"24103554-2845584-70233233","span":{"begin":2536,"end":2539},"obj":"2845584"},{"id":"24103554-19837912-70233234","span":{"begin":2587,"end":2590},"obj":"19837912"},{"id":"24103554-18837961-70233235","span":{"begin":2603,"end":2606},"obj":"18837961"},{"id":"24103554-10828853-70233236","span":{"begin":2694,"end":2697},"obj":"10828853"},{"id":"24103554-11377976-70233237","span":{"begin":2977,"end":2980},"obj":"11377976"},{"id":"24103554-19837912-70233238","span":{"begin":3078,"end":3081},"obj":"19837912"},{"id":"24103554-12759562-70233239","span":{"begin":3471,"end":3474},"obj":"12759562"},{"id":"24103554-12759562-70233240","span":{"begin":3784,"end":3787},"obj":"12759562"},{"id":"24103554-12943736-70233241","span":{"begin":3788,"end":3791},"obj":"12943736"},{"id":"24103554-20347978-70233242","span":{"begin":4021,"end":4024},"obj":"20347978"}],"text":"Cortisol regulation\nCortisol levels rise significantly during gestation and cortisol is an important hormone involved in the development of the fetus. The following sections will review cortisol regulation, physiological actions and its role in metabolic syndromes. The modulation of cortisol by the reproductive hormones and its contribution to gestational diabetes will also be discussed. Glucocorticoids such as cortisol are steroid hormones that are released by the adrenal cortex to regulate carbohydrate metabolism. The hypothalamic release of corticotrophin releasing hormone (CRH) regulates the secretion of adrenocorticotrophic hormone (ACTH) from the anterior pituitary gland, which in turn stimulates the release of cortisol from the adrenal gland. It is a tightly regulated system in which increased plasma cortisol leads to feedback inhibition of both CRH and ACTH [143]. Normal plasma levels of cortisol vary significantly according to the time of day with levels highest in the morning at 0800 h (138 to 635 mmol/L); at 1600 h the cortisol level is 83 to 413 mmol/L, and at 2000 h it is 50% of the 0800-h level. Urinary cortisol (24-h urine) in children is 5.5 to 74.0 mmol/L and in adolescents it is 14.0 to 152.0 mmol/L [139]. The human hypothalamic pituitary adrenal axis (HPA) refers to the hormonal feedback mechanisms that regulate cortisol levels in the body. The HPA is controlled with circadian rhythms [144] and ultradian rhythms with discrete pulses of ACTH and glucocorticoids to regulate cortisol levels in the body [144,145].\nAs part of the stress responses many brain regions, including the limbic and sympathetic systems, regulate HPA activity [146,147]. Serotonin can regulate the HPA axis through serotonergic pathways linked to the hypothalamus or hippocampus to stimulate CRH or ACTH release or acting as a local paracrine factor in the regulation of cortisol from the adrenal cortex [148,149]. HPA axis dysregulation is caused in part by the release of various inflammatory cytokines, including TNF-α, IL-1 and IL-6 where they stimulate CRH production [148].\nCortisol can be inactivated by the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD)-2, which is found in mineralocorticoid receptor-rich tissues such as the kidney [150] and adipose tissue [151] but not the liver. Cortisol has a high affinity for the mineralocorticoid receptor, however, inactivation to cortisone by 11β-HSD2 renders it unable to bind to the mineralocorticoid receptor and facilitates aldosterone binding to this receptor [152]. In tissues, including liver, adipose, brain [150] and blood [153], cortisol can be regenerated from its inert form, cortisone, by the enzyme 11β-HSD-1 [154]. 11β-HSD1 is a reduced nicotinamide adenine dinucleotide phosphate (NADP(H))-dependent microsomal enzyme that converts cortisone into cortisol. Expression of 11β-HSD1 can also be induced in many other tissues including fibroblasts, skeletal and smooth muscle, and immune cells [155-158]. The 11β-HSD1 enzymes are known important regulators of hormone action at the tissue level [150]. Adipocyte-derived leptin and oestrogen upregulate 11β-HSD1 [159,160] to increase both intracellular and circulating cortisol levels. In the circulation, over 90% of cortisol is bound to corticosteroid binding globulin (CBG). It is only the unbound free portion that is able to diffuse into the cell and exert its effects.\nGlucocorticoids are abundant highly widespread nuclear hormones [161,162]. They exert their actions in almost all tissues, influencing the expression of a large proportion of the human genome. Binding of the glucocorticoid to its receptor changes the transcription rates of target genes. A large number of molecules participate directly or indirectly in the signalling cascade [161,163]. Glucocorticoids are pivotal in regulating many aspects of resting and stress-related homeostasis. They are released as part of the stress response and have a catabolic effect to liberate substrates for mitochondrial oxidation [164]."}

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PMC:3852299 / 26822-30848 JSON TXT