Cortisol biosynthesis

CYP21 catalyzes steroid C21 hydroxylation required for cortisol biosynthesis. Genetic defects in this gene cause congential adrenal hyperplasia. 

Which one of the following enzymes is required for cortisol biosynthesis ... 

In congenital adrenal hyperplasia, progesterone is not hydroxylated in position 17, thus reducing cortisol biosynthesis. 

Pascoe L, Curnow KM. Genetic recombination as a cause of inherited disorders of aldosterone and cortisol biosynthesis and a contributor to genetic variation in blood pressure. Steroids 1995 60 22-7. 

Li D, Dammer EB, Sewer MB (2012) Resveratrol stimulates cortisol biosynthesis by activating SIRT-dependent deacetylation of P450scc. Endocrinology 153(7) 3258-3268... 

Cortisol biosynthesis by mitochondrial and endoplasmic reticulum enzymes of the adrenal cortex. The rate-limiting step in steroidogenesis is the importation of cholesterol from cytoplasm to mitochondria which is mediated by the steroidogenic acute regulatory protein (StAR). 

B. Inhibition of this step in cortisol biosynthesis relieves feedback inhibition of its biosynthetic enzymes, leading to accumulation of cortisol precursors, particularly 11-deoxycortisol. Normal patients will also have a compensatory increase in the secretion of ACTH. 

Ozbay, T., Merrill, A. H., Jr., and Sewer, M. B. (2004). ACTH regulates steroidogenic gene expression and cortisol biosynthesis in the human adrenal cortex via sphingolipid metabolism. Endocr Res 30, 787-794. 

The conversion of cholesterol to pregnenolone is the rate-limiting step in the biosynthesis of cortisol this conversion is stimulated by ACTH. Cortisol biosynthesis from pregnenolone involves the action of a specific reductase/ isomcrase and three separate hydroxylase enzymes. Inherited defects of all of these enzymes have been characterized. 

Aldosterone is produced exclusively by the zona glomerulosa and is primarily controlled by the renin-angiotensin system (p. 1.5). The metabolic pathway for the synthesis of aldosterone has many of the same enzymes involved in cortisol biosynthesis. The glomerular z.one lacks the 17-hydroxylase enzyme and has the additional 18-hydroxylase and 18-hydroxysteroid dehydrogenase enzymes necessary for aldosterone synthesis. 

In addition to their therapeutic uses, glucocorticoids also are used for diagnostic purposes. The overnight dexamethasone suppression test is used to determine if patients with clinical manifestations suggestive of hypercortisolism have biochemical evidence of increased cortisol biosynthesis. 

The drag metyrapone (2-methyl-l,2-di(pyridin-3-yl)propan-l-one) has been used for decades to inhibit cortisol biosynthesis, primarily through its inhibition of P450clip [83]. Metyrapone is a relatively weak inhibitor, requiring several grams per day in 3 divided oral doses. Etomidate (ethyl 1 -(1 -phenylethy 1)-1 H-iraidazole-5-car-... 

Influence of Thyroid Hormone on Cortisol Biosynthesis. A Gas Chromatographic Analysis J. Steroid Biochem. 13(4) 445-447 (1980) CA 93 92998c... 

The syndrome associated with congenital adrenal hyperplasia. In this condition there is a deficiency of one of the enzymes involved in cortisol biosynthesis. ACTH levels are therefore maximal because of the lack of feedback control in the absence of cortisol. ACTH stimulates the overproduction of androgens. This can lead to sexual precosity in the male infant and masculinization in the female. 

This is an inherited condition in which there is a deficiency of one of the enzymes of cortisol biosynthesis. The resulting low plasma cortisol levels result in high levels of ACTH production because of the absence of feedback control. This in turn results in the accumulation of androgens and cortisol precursors. The consequences of this are pseudohermaphroditism in the female child and virilization in the male child. Deficiencies of 3 -dehydrogenase, 21 -hydroxylase and 1 IjS-hydroxylase have been described. The most common is 21 -hydroxylase deficiency, in which there is abnormal sodium loss (the salt-losing syndrome), due to impaired aldosterone production. 11 -Hydroxylase deficiency results in the excess secretion of 11-deoxycorticosterone and since this is an active mineralocor-ticoid, salt and water retention and hypertension result. 

This is a metabolite of 17-hydroxyprogesterone, an intermediate in cortisol biosynthesis. It is found in increased amounts in the urine, together with its metabolite pregnanetriol, in some forms of congenital adrenal hyperplasia. 

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