Estradiol-17/3-hydroxysteroid dehydrogenase

Reactions catalyzed by 11 (3-hydroxysteroid and 17(3-hydroxysteroid dehydrogenases, (a) 11 (3-hydroxysteroid dehydrogenase type 1, an NADPH-dependent enzyme, catalyzes the conversion of the inactive steroid, cortisone, to cortisol, which is the biologically active glucocorticoid. 11 (3-hydroxysteroid dehydrogenase type 2, an NAD+-dependent enzyme, catalyzes the reverse direction, (b) 17(3-hydroxysteroid dehy-drogenase type 1, an NADPH-dependent enzyme, catalyzes the reduction of estrone to estradiol. Type 2, an NAD+-dependent enzyme, catalyzes the oxidation of estradiol to estrone. Type 3, an NADPH-dependent enzyme, catalyzes the reduction of androstene dione to testosterone. Type 4, an NAD+-dependent enzyme, catalyzes the oxidation of estradiol to estrone, and androstenediol to dehydroepiandrosterone. 

A similar mechanism has been found for 17(3-hydroxysteroid dehydrogenase (17(3-HSD), the enzyme that regulates the concentrations of estradiol and testosterone in human [5,16,17] (Figure lb). Genetics diseases associated with mutations in this enzyme lead to developmental abnormalities [18]. Enzymes that regulate the concentrations of retinoids [19] and prostaglandins [20] may also have a similar role [6]. 

Boys with 17fi-hydroxysteroid dehydrogenase deficiency fail to form testosterone from androstenedione, androstenediol fi om DHEA, or estradiol from estrone in a normal manner (see Figure 53-4). At puberty, plasma concentrations of testosterone and DHT are low, and plasma androstenedione and estrone are elevated in those individuals. ... 

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 . 

Fig. 45.3. Biosynthesis of androgens and other sex steroid hormones. The enzymes involved in this biosynthesis are (a) side-chain cleavage, (b) 17a-hydroxylase (c) 5-ene-3(3-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-reductase.

The above descr on of intrinsic fluorofdiores may seem abstract, so it seems useful to consider a specific example. The enzyme 17B-hydroxysteroid dehydrogenase (17 -HSD) catalyzes the last step in the biosyntiiesis of estradiol from estrogen. The protein consists of two identical subunits, eadi containing a sin tryptophan residue. It binds NADffl as acofactor. 

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