Steroid hormone 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. 

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... 

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. 

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... 

Buster, J. E. (1983). Gestational changes in steroid hormone biosynthesis, secretion, metabolism, and action. Clin. Perinatal. 10, 527—552. 

Steroid hormones are produced in the adrenal cortex and the sex glands. All such hormones originate from cholesterol. Figure 16.4 shows the overall scheme for steroid hormone biosynthesis that is applicable to all tissues. The final products may be divided into the following groups mineralocorticoids (e.g., aldosterone), produced by the zona glomerulosa of the adrenal cortex glucocorticoids (e.g., cortisol), produced by the zona fasciculata of the adrenal cortex and the... 

Figure 17.8 Typical hydroxylation reaction involving cytochrome P450. Ad, adrenodoxin. The substrate is a steroid hormone biosynthesis intermediate. The location of the reaction is in the mitochondria of adrenal cortex. (Reproduced by permission from Bezkorovainy A. Biochemistry of Nonheme Iron. New York Plenum Press, 1980, p. 380.)...

Bishop, G.J. (2007) Refining the plant steroid hormone biosynthesis pathway. Trends Plant Sci. 12, 377-80. 

Conversion of cholesterol to pregnenolone is the rale-limiting step in steroid hormone biosynthesis. It is not ihccnry-malic transformation itself that is rate limiting, however, the translocation of cholesterol to the inner milochondrui membrane of steroid-synihesi/.ing cells is rate limiting. A key protein involved in the translocation is the 5Kruidugcmc... 

Simpson ER, Waterman MR. Steroid hormone biosynthesis in the adrenal cortex and its regulation by adrenocorticotropin. In Besser M, Burger HG, Jameson JL, eds. Endocrinology 3rd ed. Philadelphia WB Saunders Co, 1995 1630-41. 

Sanderson JT (2006) The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals. Toxicol Sci 94(1) 3-21... 

Cholesterol and many of its biosynthetic precursors are highly insoluble in aqueous media. Yet, cholesterol biosynthesis, utilization and intracellular transfers occur in environments which involve both aqueous and nonaqueous components. For example, the enzymes involved in the conversion of squalene to cholesterol, the conversion of cholesterol to cholesterol esters, and the conversion of cholesterol to 7a-hydroxycholesterol are associated with the endoplasmic reticulum (microsomes). The conversion of cholesterol to pregnenolone, an essential first step in steroid hormone biosynthesis, occurs in mitochondria. In addition, transfers of cholesterol from cytoplasmic lipid inclusion droplets through the cytosol to the mitochondria are essential for steroid hormone production. 

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