Hormone glucocorticoids

The discovery in 1954 that fluorination of the glucocorticoid hormone cortisol could bring about remarkable changes in the biological properties of the hormone was entirely unexpected and violated the then prevalent belief that synthetic variants could not surpass a naturally occurring hormone in its biological activity. Because of the impact that fluorination of steroids has had on subsequent developments in this area the history of the discovery of fluorocortisol will be briefly recounted. 

An endocrine disorder first described by the British Physician Thomas Addison in the mid 1800 s. The adrenal glands fail to produce sufficient amounts of glucocorticoid hormones (cortisol) and sometime mineralocorticoid (aldosterone). If left untreated it is life-threatening, the patient will show muscle weakness, hyperpigmentation and even depression. Typical treatment is hydrocortisone replacement therapy. 

Endogenous antipyretics include certain cytokines, neuropeptides, glucocorticoids, hormones, nitric oxide, and others. 

PNMT catalyzes the N-methylation of norepinephrine to form epinephrine in the epinephrine-forming cells of the adrenal medulla. Since PNMT is soluble, it is assumed that norepinephrine-to-epinephrine conversion occurs in the cytoplasm. The synthesis of PNMT is induced by glucocorticoid hormones that reach the medulla via the intra-adrenal portal system. This special system provides for a 100-fold steroid concentration gradient over systemic arterial blood, and this high intra-adrenal concentration appears to be necessary for the induction of PNMT. 

A second explanation of the ability of oxidative stress to cause DNA damage is that the stress tri ers a series of metabolic events within the cell that lead to activation of nuclease enzymes, which cleave the DNA backbone. Oxidative stress causes rises in intracellular free Ca, which can fiagment DNA by activating Ca -dependent endonucleases (Orrenius etal., 1989 Farber, 1990 Ueda and Shah, 1992) in a mechanism with some of the features of apoptosis (see Wyllie, 1980). An example of apoptosis is the killing of immature thymocytes by glucocorticoid hormones, which activate a cell-destructive process that apparently involves DNA fragmentation by a Ca -dependent nuclease. 

Like all steroids, aldosterone enters the target cell and combines with cytosolic mineralocorticoid receptor. Such receptors are not entirely specific for aldosterone and will also bind cortisol, the principal glucocorticoid hormone. The receptors are protected from cortisol activation by 11 3 hydroxysteroid dehydrogenase which... 

Patient dependent on therapeutic effect Antiarrhythmics Antiepileptics Glucocorticoids Hormonal contraceptives... 

Current theories suggest that hypersecretion of cortisol during stress may damage the hippocampus. Studies have demonstrated reduced hippocampal volume in trauma survivors with PTSD, compared to nontrauma tized individuals (Sapolsky, 2000 Bremner, 2001). However, hormonally regulated plasticity in the hippocampus involves multiple influences, and glucocorticoid hormones work in concert with excitatory amino acids and N-methyl-D-aspartate (NMDA) receptors, as well as other neurotransmitters and the GABA-benzodiazepine system (see McEwen, 2000a,b, for review). 

Examples discussed in this book include digitalis glycosides, which act by inhibiting Na+,K+ ATPase in cell membranes methotrexate, which inhibits the enzyme dihydrofolate reductase and glucocorticoid hormones. 

Glucocorticoid hormones alter bone mineral homeostasis by antagonizing vitamin D-stimulated intestinal calcium transport, by stimulating renal calcium excretion, and by blocking bone formation. Although these observations underscore... 

Aldosterone exerts its effects on the kidneys by binding to specific receptors in epithelial cells that line the distal tubule of the nephron.18 These receptors have a high affinity for mineralocorticoid hormones. They also have a moderate affinity for many of the natural glucocorticoid hormones (e.g., cortisol) and a low... 

All forms of stress result in the activation of the pituitary-adrenal axis, with a consequent rise in circulating catecholamines and glucocorticoid hormones from the adrenal gland. The secretion of ACTH from the pituitary gland, which is controlled by hypothalamic CRF, triggers the secretion of adrenal glucocorticoids, while stress-induced activation of... 

---