Hormones biosynthesis

Most of these enzymes have steroids or fatty acids as their substrates (Table 1). Many P450s in endogenous biotransformation pathways are characterized by usually very narrow substrate and product specificity and by tight regulatory systems, especially those involved in steroid hormone biosynthesis. 

Miller WL Molecular biology of steroid hormone biosynthesis. EndocrRev 1988 9 295. 

Stocco, D. M. 2001. StAR protein and the regulation of steroid hormone biosynthesis. Annu. Rev. Physiol., 63 193-213. 

Iodide acutely blocks thyroid hormone release, inhibits thyroid hormone biosynthesis by interfering with intrathyroidal iodide use, and decreases the size and vascularity of the gland. 

Brevioxime 25 is a natural product isolated from Penicillum brevicompactum and displays in vitro inhibition of juvenile hormone biosynthesis. Two different synthetic approaches have been described for this molecule. Different authors carried out the cyclization of the unsaturated ketoamide 409 in the presence of nitrosyl chloride that directly produced cyclization and led to the oxime <2001SL257, 2001T8699>. Starting from the same... 

In addition, it will be our intention to present a deeper insight into the biosynthesis of steroid hormones, which will allow definition of new targets and approaches for the treatment of endocrine-responsive cancer. Enzymes involved in mechanisms of steroid hormone biosynthesis might be novel targets for endocrine therapy. Moreover, further therapeutic indications for modulators of steroid hormone receptors will be discussed. In summary, many promising new opportunities for endocrine therapy of breast and prostate cancer are now arising. 

Enzymes that are involved in steroid hormone biosynthesis or in steroid metabolism are also targets of anti-hormonal therapy. Recently, it was discovered that certain co-factors modulate the signalling of steroid hormone receptors in a tissue-selective fashion. By binding the receptor ligand complex, these co-activators and co-repressors are capable of either activating or repressing transcription, respectively [5j. 

Hormone Deprivation - Inhibition of Steroid Hormone Biosynthesis... 

Biosynthesis represents the major metabolic fate of cholesterol, accounting for more than half of the 800 mg/day of cholesterol that the average adult uses up in metabolic processes. By comparison, steroid hormone biosynthesis consumes only about 50 mg of cholesterol per day. Much more that 400 mg of bile salts is required and secreted into the intestine per day, and this is achieved by recycling them. Most of the bile salts secreted into the upper region of the small intestine are absorbed along with the dietary lipids that they emulsified at the lower end of the small intestine. They are... 

Diets rich in millet have been associated with endemic goiter in parts of West Africa where millet is a staple. The damage has been attributed to vitexin, a C-glycosyl flavone, that in rats has antithyroid activity and that in vitro inhibits thyroid peroxidase and the free radical iodination step in thyroid hormone biosynthesis. Isoflavones have produced similar antithyroid effects in rats, but clinical studies in adults have not. " However, this remains a possible concern in infants fed soya-based milk-replacers, especially if iodine supply is compromised. 

The first committed step in the synthesis of triterpenoid saponins involves the cyclisation of 2,3-oxidosqualene to give one of a number of different potential products [9]. Most plant triterpenoid saponins are derived from oleanane or dammarane skeletons, although lupanes are also common [9]. This cycHsation event forms a branchpoint with the sterol biosynthetic pathway, in which 2,3-oxidosqualene is cyclised to lanosterol (in animals and fungi) or to cycloartenol (in plants) (Fig. 2). Sterols are important membrane constituents and also serve as precursors for hormone biosynthesis. 

Figure 3. Outline of juvenile hormone biosynthesis based on Ref. 23.

Cytochromes P450 form a very large group of heme enzymes that catalyze the hydroxylation of a variety of substrates. They are important in drug metabolism, in cholesterol and steroid hormone biosynthesis, and in numerous other pathways. They have been found to participate in reactions other than hydroxyla-tions. 

Biosynthesis of thyroid hormones. The sites of action of various drugs that interfere with thyroid hormone biosynthesis are shown... 

Outline of major pathways in adrenocortical hormone biosynthesis. The major secretory products are underlined. Pregnenolone is the major precursor of corticosterone and aldosterone, and 17-hydroxypregnenolone is the major precursor of cortisol. The enzymes and cofactors for the reactions progressing down each column are shown on the left and across columns at the top of the figure. When a particular enzyme is deficient, hormone production is blocked at the points indicated by the shaded bars. 

Gadot, M., Burns, E. and Schal, C. (1989). Juvenile hormone biosynthesis and oocyte development in adult female Blattella germanica effects of grouping and mating. Archives of Insect Biochemistry and Physiology 11 189-200. 

Ascorbic acid may be required for steroid hormone biosynthesis depleted from adrenal cortex on cortical secretion Biotin adrenocortical insufficiency noted in biotin deficiency... 

Stereospecific 2,3-epoxidation of squalene. followed by a non-concerted carbocationic cyclization and a seiies of carbocationic rearrangements, forms lanosterol (26) in the first steps dedicated solely toward steroid synthesis. Cholesterol is the principal starting material for steroid hormone biosynthesis ill animals. The cholesterol biosynthetic pathway is composed of at least 30 enzymatic reactions. Lanosterol and squalene appear to he normal constituents, in trace amounis. in tissues that are actively synthesizing cholesterol,... 

The initial reaction in steroid hormone biosynthesis is catalyzed by desmolase (side-chain cleavage complex), which is found in the mitochondria of steroid-producing tissues (e.g., adrenals, gonads). The reaction is shown in figure 20.22. The product, pregnenolone, is subsequently transferred to the endoplasmic reticulum, where an oxidation of... 

A large number of diseases are due to either overproduction or underproduction of hormones, or to insensitivity of target tissues to circulating hormones. Knowledge of hormone biosynthesis, secretion, and interaction with target cells is essential to an understanding of the biochemical basis of these disorders. 

The primary steps in thyroid hormone biosynthesis are shown schematically in Figure 31-2. Thyroid follicle cells take up and concentrate iodide from the bloodstream—this is significant because there must be a sufficient amount of iodine in the diet to provide what is needed for thyroid hormone production.55 Thyroid cells also manufacture a protein known as thy-... 

FIGURE 31-2 Thyroid hormone biosynthesis. Iodide is taken into the follicle cell, where it is converted by thyroid peroxidase to an oxidized form of iodine (Ip). h is transported to the follicle lumen, where it is bonded to tyrosine residues of the thyroglobulin [TGB] molecule. Iodinated TGB is incorporated back into the cell, where it undergoes lysis to yield the thyroid hormones T3 and T4. See text for further discussion. 

Iodide. Relatively large dosages of iodide (exceeding 6 mg/d) cause a rapid and dramatic decrease in thyroid function.35 In sufficient amounts, iodide inhibits virtually all the steps involved in thyroid hormone biosynthesis. For instance, high iodide levels limit the uptake of iodide into thyroid follicle cells, inhibit the formation of T4 and T3, and decrease the secretion of the completed hormones from the thyroid cell. 

Outline of major pathways in adrenocortical hormone biosynthesis. The major secretory products are underlined. Pregnenolone is the major precursor of corticosterone and aldosterone, and 17-... 

Schooley D. A. and Baker F. C. (1985) Juvenile hormone biosynthesis. In Comprehensive Insect Physiology, Biochemistry, and Pharmacology, eds G. A. Kerkut, and L. I. Gilbert, Vol. 7, pp. 363-389. Pergamon Press, Oxford. 

Taub-Montemayor T. E. Dahm K. H., Govindan B. and Rankin M. A. (1997a) Rates of juvenile hormone biosynthesis and degradation during reproductive development and diapause in the boll weevil, Anthonomus grandis. Physiol. Entomol. 22, 269-276. 

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