Steroid hormone production, secondary

Among the various classes of natural products, perhaps none is as extensive as the collection of structures that derive ifom the union and rearrangement of terpene building blocks. Indeed, whether in the form of a relatively small compound such as pinene or a far more complex and biochemically relevant steroid hormone, these secondary metabohtes are ubiquitous throughout Nature. Despite their widespread presence, however, their structures are far from ordinary, as many possess molecular architectures so exotic that even the most inventive of chemists would have a hard time imagining them prior to their full structural elucidation. 

Reproductive organs are the primary source of the steroid hormones that influence sexual and reproductive functions. In men, the testes produce testosterone and similar androgens that are responsible for spermatogenesis and the secondary sexual characteristics of adult males.7,26 In women, sexual maturation and reproductive function are governed by the production of estrogens and progestins from the ovaries.27 The release of male and female sex steroids is controlled by hormones from the hypothalamus and anterior pituitary.32 The control of male and female hormone activity and the pharmacologic implications of these hormones are discussed in Chapter 30. 

The adrenal cortex (AC) produces the glucocorticoid cortisol (hydrocortisone) in the zona fasciculata and the mineralocorticoid aldosterone in the zona glomerulosa. Both steroid hormones are vitally important in adaptation responses to stress situations, such as disease, trauma, or surgery. Cortisol secretion is stimulated by hypophyseal ACTH aldosterone secretion by angiotensin II in particular (p. 128). In AC failure (primary adrenocortical insuf ciency, Addison disease), both cortisol and aldosterone must be replaced when ACTH production is deficient (secondary adrenocortical insuf ciency), cortisol alone needs to be replaced. Cortisol is effective when given orally (30 mg/day, 2/3 a.m 1 /3 p.m.). In stress situations, the dose is raised 5- to 10-fold. Aldosterone is poorly effective via the oral route instead, the mineralocorticoid fludrocortisone (0.1 mg/day) is given. 

More recent studies also suggest that increased IL-6 production is associated with age-related depression (D6) and disability due to muscle atrophy and/or various specific diseases (F8). Moreover, Straub et al. (S30) suggest that increased IL-6 levels may be secondary to diminished levels of the steroid hormone, dehy-droepiandrosterone (see below under neuroendocrine aging theory). The pathophysiologic role of IL-6 in human disease has been recently reviewed (P7). 

Poly(c -l,4-isoprene) belongs to the family of polyisoprenoids, which are the most structurally diverse and abundant natural products known, with more than 23,000 primary and secondary metabolites. This huge family comprises, for example, sterols which display not only structural functions (control of biological membrane fluidity) but also hormonal functions (steroid hormones). Key phyto-hormones, such as abscisic acid, gibberellins and cytokinins, are isoprenoids too. Moreover, isoprenoids are used in protein prenylation, which is a key step in the activation and the localization of metabolic enzymes in many organisms. The first common step of all isoprenoid biosynthesis pathways is the formation of isopentenyl diphosphate (IPP). ... 

Limonene as a by-product of orange juice production can be used for polymer production together with CO2 to form a polystyrol-like foam. Menthon can be used as a precursor for branched dicarbonic acids and alpha-pinen (a by-product of the forest industry) as precursor for cymol production or for enzymatic verbenone production. Other important terpenoids are phytosterols. They are used in the production of steroid hormones such as cortison or progesteron by Bayer Sobering Pharma. Probably the most important example where plant secondary metabolism and microbial fermentation are synergistically combined, steroid hormones, are produced from phytosterols. A fermentation process by Bayer Schering Pharma uses a plant metaboUte and converts it by a single-step microbial fermentation into the desired end product. 

Makin, H. L. J. (ed.) Biochemistry of Steroid Hormones. Blackwell, Oxford 1975 Roddick, J. G. Isoprenoid alkaloids. In Encyclopedia of Plant Physiology, New Series, Vol. 8, Secondary Plant Products (E. A. Bell, B. V. Charlwood, eds.), pp. 167-184. Springer, Berlin-Heidelherg-New York 1980... 

In animals for instance steroid hormones (D 6.4.5-D 6.4.7), porphyrins (D 10.1) and epinephrine (D 22.1.1) are transformed to other secondary products which may be excreted more easily and are removed from the body with urine or bile (Table 60). 

In animals hormones are either formed de novo from substances of primary metabolism, e.g., steroid hormones, epinephrine, tyroxin, or they are synthesized from special secondary products which have to be taken up with the diet, e.g., unsaturated fatty acids (vitamins F) which are precursors of the eicosanoids. 

See also Withdrawal of corticosteroid pharmacotherapy, below) This occurs in patients who have recently received prolonged pharmacotherapy with a corticosteroid which inhibits h)rpothalamic production of the corticotropin releasing hormone and so results in secondary adrenal failure. It is treated by reinstituting therapy or as for acute insufficiency, as appropriate. To avoid an acute crisis on stopping, steroid therapy must be withdrawn gradually to allow the hypothalamus. 

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