**2. 17hydroxysteroid dehydrogenases**

The 17-hydroxysteroid dehydrogenases (17-HSDs) belong to the short-chain dehydrogenase reductase (SDR) protein superfamily, which also includes the 3 hydroxysteroid dehydrogenase (3HSD). These enzymes regulate the levels of bioactive steroid hormones in many tissues and they are expressed not only in genital tissues, which are the primary target, but also in peripheral blood. The 17-HSDs, along with other steroid

17β-Hydroxysteroid Dehydrogenase Type 3 Deficiency:

liver, ovary, mammary glands and placenta

placenta, liver, intestine, endometrium, kidney, prostate,

pancreas

mainly testes, adipose tissue, brain, sebaceous glands and bone

liver, heart, prostate, testes, lung, skeletal muscle, kidney, pancreas, thymus, ovary,intestine, placenta and breast

cancer lines

and liver

placenta, testes, prostate, adrenals

widespread, liver, kidney, ovary,

widespread, liver, CNS, kidney, testes

testes

**Type of 17-HSD (Gene Name)** 

17-HSD type 1 (HSD17B1)

17-HSD type 2 (HSD17B2)

17-HSD type 3 (HSD17B3)

17-HSD type 4 (HSD17B4)

17-HSD type 5 (AKR1C3)

17-HSD type 6 (HSD17B6/RODH)

17-HSD type 7 (HSD17B7)

17-HSD type 8 (HSD17B8)

17-HSD type 9 (HSD17B8/RDH5)

17-HSD type 10 (HSD17B10)

Diagnosis, Phenotypic Variability and Molecular Findings 121

E2

FA

not determined only retinoid metabolism

not determined cholesterol synthesis;

E2

not determined only retinoid metabolism

**Locations Functions Cofactor/** 

catalyzes the

interconversion of E1 to

inactivates both E2 into E1 and T into 4-A

inactivates both E2 into E1, and 5-diol into DHEA-; oxidation of

converts4-A to T in peripheral tissues; bile acid production and detoxification; eicosanoid synthesis

identified in humans

interconversion of E1 to

possible role in fatty acid metabolism; inactivates both E2 into E1 and

identified in humans

oxidation of fatty acids; catalyzes the synthesis of

androstane-3, 17diol; oxidation of the 21OH groups on C21 steroids

catalyzes the

androgens

DHT from 5-

converts4-A to T NADPH/

**reactions** 

NADPH/ reduction

NAD+/ oxidation

reduction

NAD+/ oxidation

NADPH/ reduction

NAD+/ oxidation

NADPH/ reduction

NAD+/ oxidation

not determine

d

NAD+/ oxidation **Gene location** 

17q21.2

16q23.3

9q22.32

5q23.1

10p15.1

12q13.3

10p11.2 1q23

6p21.32

12q13.2

Xp11.22

metabolizing enzymes such as aromatase, steroid sulfatase, 3-HSD and 5-reductase are able to produce their own hormones at the peripheral cells (intracrine activity). In steroidogenic tissues (the gonads and adrenal cortex) they catalyze the final step in androgens, estrogens and progesterone byosinthesis; in peripheral tissues, they convert active steroid hormones into their metabolites, and regulate hormone binding to their nuclear receptor. So far, 14 17HSDs have been characterized in mammals, which show little amino acid homology but that are all members of the SDR family, with the exception of 17-HSD type 5 (17-HSD5) which is an aldo-keto reductase (Lukacik et al., 2006; Luu The, 2001; Prehn et al., 2009). These isoenzymes differ as regards tissue-specific expression, catalytic activity, substrate and cofactors specificity (NAD/NADH *vs* NADP/NADPH), and subcellular localization (Payne § Hales, 2004). Although *in vitro* they act both as reductase or as oxidase enzymes, *in vivo* they work in a predominat one-way, or reductive or oxidative, converting inactive 17-ketosteroids in their active 17-hydroxy forms (Khan et al., 2004). Thus, they can be grouped into *in vivo* oxidative enzymes (17-HSD types 2, 4, 6, 8, 9, 10, 11 and 14) and *in vivo* reductive enzymes (17-HSD types 1, 3, 5 and 7).
