[5-alpha-reductases: physiology and pathology].
In most androgen target tissues, the first step of androgen action is the 5 alpha-reduction of testosterone to DHT which binds to the androgen receptor with an affinity 3 to 4 fold higher than testosterone. Two genes, encoding two isozymes of 5 alpha-reductase (5 alpha-R) have been cloned. The two isoforms, 5 alpha-R1 and 5 alpha-R 2 are located on chromosomes 5 and 2 respectively and differ in optimal pH, substrate and inhibitor affinities and tissue expression. 5 alpha-R 2 is responsible for sexual differentiation. It is the major form expressed in the prostate where it seems necessary for embryonic growth and development. 5 alpha-reductase deficiency results in androgen insensitivity due to abnormal 5 alpha-R 2. Affected patients are XY individuals with a very peculiar form of male pseudohermaphroditism: they have feminine genitalia at birth and masculinize at puberty. 29 mutations, spanning the whole coding portion of the gene, have been described; correlation between mutations and enzyme activity have led to the suggestion that both the N- and the C-terminal end of the gene are involved in substrate binding, whereas the cofactor binding-site is located in the C-terminus. In contrast to androgen insensitivity due to 5 alpha-reductase deficiency, increased 5 alpha-reductase activity can result in androgen hypersensitivity as described in idiopathic hirsutism or benign prostatic hyperplasia. In these case 5 alpha-R 1 could possibly be involved.
Mowszowicz
I
I
Laboratoire de Biochimie, Hôpital Necker, Paris.
Berthauit
I
I
Mestayer
C
C
Wright
F
F
Kuttenn
F
F
Mauvais-Jarvis
P
P
D042944:Cholestenone 5 alpha-Reductase; D012734:Disorders of Sex Development / Q000201:enzymology; D005260:Female; D006628:Hirsutism / Q000201:enzymology; D006801:Humans; D008297:Male; D010088:Oxidoreductases / Q000172:deficiency / Q000378:metabolism*; D011467:Prostate / Q000201:enzymology; D011470:Prostatic Hyperplasia / Q000201:enzymology; D012867:Skin
D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase
Les 5 alpha-réductases: physiologie et pathologie.