Type 5 17 beta-hydroxysteroid dehydrogenase: its role in the formation of androgens in women

Type 5 17 beta -HSD, one of the seven types of 17 beta -hydroxysteroid dehy drogenase (17 beta -HSD) so far characterized in humans, catalyzes the tran sformation of 4-androstenedione (4-dione) into testosterone (T). This react ion is also catalyzed by type 3 17 beta -HSD which is responsible for pseud ohermaphroditism in deficient man but is asymptomatic in deficient women. S ince type 3 17 beta -HSD is not found in the ovary, whereas type 5 is. it i s suggested that the latter is involved in the conversion of 4-androstenedi one to testosterone in the ovary. The comparison of type 5 17 beta -HSD of different species shows that the human enzyme shares 95 and 78% identity wi th the monkey and mouse enzymes respectively. In addition, the human and mo nkey enzymes are labile and are destroyed upon homogenization of the transf ected cells, whereas the mouse enzyme is not. Human type 5 17 beta -HSD als o possesses a high 20 alpha -HSD activity that inactivates progesterone, wh ereas the monkey and mouse enzymes do not have such high 20 alpha -HSD acti vity. Since the endocrine ovary is composed of two types of cells. one prod ucing androgens (theca cells) and the other producing progesterone and estr ogens (granulosa cells), it is tempting re, suggest that the role of the hi gh 20 alpha -HSD activity of type 5 17 beta -HSD is to protect the theca ce lls against the progesterone produced by the granulosa cells. The double ac tivity of type 5 17 beta -HSD in the female reproductive tissues is probabl y necessary to the control of the optimal level of progesterone and sex ste roids. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.