3p-Hydroxysteroid dehydrogenase

Finsterbusch, A., Lindemann, R, Grimm, R., Eckerskom, C. and Luckner, M. (1999) A(5)-3p-hydroxysteroid dehydrogenase from Digitalis lanata Ehrh. - a multifunctional enzyme in steroid metabolism Planta, 209,478-86. 

Herl, V., Frankenstein, J., Meitinger, N., Miiller-Uri, F. and Kreis, W. (2007) A 5-3p-hydroxysteroid dehydrogenase (3p HSD) from Digitalis lanata. Heterologous expression and characterisation of the recombinant enzyme. Planta Med., 73, 704-10. 

Trilostane blocks the synthetic path earlier (3p-hydroxysteroid dehydrogenase) and thus also inhibits aldosterone synthesis. 

Cortisol is synthesized from pregnenolone by two pathways in the fasciculata and reticularis zones of the adrenal gland. For simplicity, only one pathway is shown in Figure 51-6. The enzyme 17a-hydroxylase and the enzyme complex A -3P-hydroxysteroid dehydrogenase A ketosteroid isomerase located in the endoplasmic reticulum will synthesize 17a-hydroxyprogesterone from either 17a-hydroxypregnenolone or progesterone. Hydroxylation of this compound by the... 

II A5-3p-Hydroxysteroid dehydrogenase and A5-ketosteroid isom erase in 21-Hydroxylase IV Up-Hydroxylase... 

Figure 51-15 Formation of steroids in patients with adrenogenital syndrome caused by 21 -hydroxylase deficiency. Bold lettering indicates steroids that are found elevated in the circulation. ACTH, Adrenocorticotropic hormone SpSDH 3p-hydroxysteroid dehydrogenase.

Classical congenital hyperplasia 21-Hydroxylase deficiency 11-Hydroxylase deficiency 3P-Hydroxysteroid dehydrogenase deficiency Adult or attenuated adrenal hyperplasia Androgen-producing adrenal tumors... 

Norethynodrel, I7-a-ethinyl-17p-hj roxy-5(10)-estrene-3-one, increases eidrenal wei ts in intact female rats59. plasma and adrenal B levels decrease at the time of day dien values are normally highest. Clomiphene increases output of 17-oxysteroids in a patient with galactorrhea Cyano-trimethylandrostenolone, 2a-cyano-J4-, k, 17a-trimethyl-17p -OH- 5-androstene- 3-one, causes adrenal hypertrophy, a fall in adrenal venous 3 of male rats and inhibition of 3P-hydroxysteroid dehydrogenase l. Norethandrolone, 170(-ethyl-17P-0H- -norandrostene-3-one, stimulates the production of B by adrenals of castrated rats and increases pituitary ACTH content . This androgen partially reverses the E induced suppression of B production but not of the adrenal response to stresses. Testosterone, androstenedione, EHEA, estrone and estradiol has no effect on conversion of B to 18-OH B and Aldo by sheep adrenal mitochondria . 

F. 34.24. Cellular route for cortisol synthesis. Cholesterol is synthesized from acetyl CoA or derived from low-density lipoprotein (LDL), which is endoc5hosed and digested by lysosomal enzymes. Cholesterol is stored in cells of the adrenal cortex as cholesterol esters. ACTH signals the cell to convert cholesterol to cortisol. 1 = cholesterol desmolase (involved in side chain cleavage) 2 = 3p-hydroxysteroid dehydrogenase 3 = 17a-hydroxylase 4 = 21-hydroxylase 5 = 11 P-hydroxylase. 

Fig. 46.3. Biosynthesis of sex steroid hormones. The enzymes involved in this biosynthesis are (a) side-ohain cleavage, (b) 17a-hydroxylase, (o) 5-ene-3p-hydroxysteroid dehydrogenase, (d) 3-oxosteroid-4,5-isomerase, (e) 17,20-lyase, (f) 17(3-hydroxysteroid dehydrogenase, (g) aromatase, (h) estradiol dehydrogenase, and (i) 5a-reduotase.

Activation of the LH receptor results in an increase of intracellular cyclic adenosine monophosphate (cAMP) levels via activation of a G protein and adenylate cyclase. In the presence of elevated concentrations of cAMP, cholesterol esterase activation occurs. This enzyme catalyzes the cleavage of cholesterol esters to free cholesterol, v/hich is then converted in mitochondria to pregnenolone as described previously. The formation of progesterone from pregnenolone is catalyzed by 5-ene-3p-hydroxysteroid dehydrogenase and 3-oxosteroid-4,5-isomerase (steps c and d in Fig. 46.3). 

The development of analytical assays enabling the comprehensive detection of AAS in sports drug testing samples has required the consideration of the commonly rather extensive metabolism of these xeno-biotics. Principle metabolic reactions of synthetic anabolic steroids are closely related to those reported for testosterone (see section 6.1.2.2), with major pathways controlled by various enzymes such as members of the cytochrome P450 system, 17 3-hydroxysteroid dehydrogenase, 3a-/3P-hydroxysteroid dehydrogenase and 5a-reductases, which are primarily responsible for the conversion of testosterone into active... 

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