Hormones cortisol

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. 

It grew out of another discovery in the senior author s laboratory, namely, that Reichstein s compound S could be converted in high yield into 11-epicortisol (1) by the enzymes of fungi of the genus Aspergillus The conversion of this inactive substance into the hormone cortisol thus became a problem of considerable importance. A route involving the 9,11-dehydro steroid (3) readily prepared from 11-epicortisol via its 21-acetate 11-tosylate... 

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. 

A trophic hormone acts on another endocrine gland to stimulate secretion of its hormone. For example, thyrotropin, or thyroid-stimulating hormone (TSH), stimulates the secretion of thyroid hormones. Adrenocorticotropin, or adrenocorticotropic hormone (ACTH), stimulates the adrenal cortex to secrete the hormone cortisol. Both trophic hormones are produced by the pituitary gland in fact, many trophic hormones are secreted by the pituitary. The pituitary gland is sometimes referred to as the "master gland" because its hormones regulate the activity of other endocrine glands. 

In skeletal muscle, glucose transport is non-equilibrium, so that an increase in activity of the transporter increases glucose utilisation. Factors that increase the activity of the transporter (e.g. the number of transporter molecules) in the membrane are insulin and sustained physical activity. In contrast, the hormone cortisol decreases the number of transporters in the membrane. This decreases glucose uptake and is one of the effects of cortisol that helps to maintain the normal blood glucose level (Chapter 12). 

The hormone cortisol is lip, 17a, 21-trihydroxy-4-pregnene-3,20 dione. It is the major glucocorticoid synthesised and secreted by the human adrenal cortex. Cortisol enters the cell then binds to its receptor. The cortisol-receptor complex enters the nucleus and binds to DNA. 

In relatively recent years, it has become clear that under-nntrition of mother leads to low birth weight of the baby and this can increase the risk of development of degenerative disease in later life, e.g. hypertension, obesity, type 2 diabetes. One hypothesis is that the foetus adapts meta-bolically to deficiencies by increasing the number of cells in organs that perform specific functions that can overcome the deficiency, e.g. an increase in the number of liver cells that carry out gluconeogenesis, an increase in cells in the adrenal cortex to produce more of the chronic stress hormone, cortisol. These changes are carried over into adnlthood which can lead to an inadequate response of the liver to insulin so that insulin resistance develops. So far, however, it is unclear whether deficiencies in specific nntrients or undemutrition per se are responsible for snch changes (Chapter 15). 

The synthesis and degradation of muscle proteins are regulated by hormones. Cortisol leads to muscle degradation, while testosterone stimulates protein formation. Synthetic anabolics with a testosterone-like effect have repeatedly been used for doping purposes or for intensive muscle-building. 

Many steroid hormones are regulated by this type of axis—e.g., thyroxin, cortisol, estradiol, progesterone, and testosterone. In the case of the glucocorticoids, the hypothalamus releases corticotropin-releasing hormone (CRH or corticoliberin, a peptide consisting of 41 amino acids), which in turn releases corticotropin (ACTFl, 39 AAs) in the pituitary gland. Corticotropin stimulates synthesis and release of the glandular steroid hormone cortisol in the adrenal cortex. 

Most attempts of using hormones as psychotropic medications were conducted with gonadal or with thyroid hormones, mainly because of the apparent mood changes associated with physiological or disorder-associated changes in levels or activity of these hormones. However, as shown in Table 17-1, current applications are broader and involve several hormones and systems. It is anticipated that, with acquired knowledge on mood effects of several other hormones, that list will continue to expand. Here, I focus on psychotropic effects of gonadal and thyroid hormones. Cortisol and melatonin are only briefly discussed. 

The structure-activity relationships of glucocorticoids are based on two natural hormones, cortisol (3.8) and corticosterone (5.61). The characteristic structural features of these hormones are the conjugated 3-ketone, the 11-OH group, and the up-ketol side chain. Molecular modifications have been aimed at deriving compounds with glucocorticoid... 

Muller H, Hiemke C, Hammes E, Hess G. Sub-acute effects of interferon-alpha 2 on adrenocorticotrophic hormone, cortisol, growth hormone and prolactin in humans. Psychoneuroendocrinology 1992 17(5) 459-65. 

One interesting theory within the weight loss industry is that hormones cause fat to gather around the abdomen. The companies that make Relacore, CortiSlim, and their competitors claim their products lower the body s levels of the hormone cortisol. This is the hormone that the body produces when a person is under stress. 

Redwine L, Hauger RL, Gillin JC, Irwin M. Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans. J Clin Endocrinol Metab 2000 85 3597-3603. 

Metabolites and substrates (cholesterol, creatinine, glucose, uric acid), hormones (cortisol, progesterone), electrolytes (Li, Na, K, Mg, Ca, Cl)... 

Target organ T4/T3 hormone Cortisol Oestradiol Testosterone IGF-1... 

Induction of Tryptophan Dioxygenase by Glucocorticoid Hormones The de novo synthesis of tryptophan dioxygenase is induced by glucocorticoid hormones (cortisol in human beings and corticosterone in the rat). This is true induction of new mRNA and protein synthesis indeed. 

Oskam I, Ropstad E, Lie E, et al. Organochlorines affect the steroid hormone cortisol in free-ranging polar bears (Ursus maritimus) at Svalbard, Norway. J Toxicol Environ Health 2004 67(12) 959 77. 

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