Type 5 17beta-hydroxysteroid dehydrogenase: its role in the formation of androgens in women.
Type 5 17beta-HSD, one of the seven types of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) so far characterized in humans, catalyzes the transformation of 4-androstenedione (4-dione) into testosterone (T). This reaction is also catalyzed by type 3 17beta-HSD which is responsible for pseudohermaphroditism in deficient man but is asymptomatic in deficient women. Since type 3 17beta-HSD is not found in the ovary, whereas type 5 is, it is suggested that the latter is involved in the conversion of 4-androstenedione to testosterone in the ovary. The comparison of type 5 17beta-HSD of different species shows that the human enzyme shares 95 and 78% identity with the monkey and mouse enzymes respectively. In addition, the human and monkey enzymes are labile and are destroyed upon homogenization of the transfected cells, whereas the mouse enzyme is not. Human type 5 17beta-HSD also possesses a high 20alpha-HSD activity that inactivates progesterone, whereas the monkey and mouse enzymes do not have such high 20alpha-HSD activity. Since the endocrine ovary is composed of two types of cells, one producing androgens (theca cells) and the other producing progesterone and estrogens (granulosa cells), it is tempting to suggest that the role of the high 20alpha-HSD activity of type 5 17beta-HSD is to protect the theca cells against the progesterone produced by the granulosa cells. The double activity of type 5 17beta-HSD in the female reproductive tissues is probably necessary to the control of the optimal level of progesterone and sex steroids.
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Medical Research Council Group in Molecular Endocrinology, Oncology and Molecular Endocrinology Research Center, Laval University Hospital (CHUL) and Laval University, 2705 Laurier Boulevard, G1V 4G2, Quebec, Canada. van.luu-the@crchul.ulaval.ca
Dufort
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Pelletier
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Labrie
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D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D015089:20-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D000728:Androgens / Q000096:biosynthesis*; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D004795:Enzyme Stability; D019143:Evolution, Molecular; D005260:Female; D000882:Haplorhini; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D010053:Ovary / Q000201:enzymology; D017385:Sequence Homology; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D007527:Isoenzymes; D013739:Testosterone; D000735:Androstenedione; D015067:17-Hydroxysteroid Dehydrogenases; D015089:20-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase