**2.3 17-hydroxisteroid dehydrogenase type 3**

17-hydroxisteroid dehydrogenase type 3 (17-HSD3) isoenzyme catalyzes the reductive conversion of the inactive C-19 steroid, 4-A, into the biologically active androgen, T, in the Leydig cells of the testes (Payne § Hales, 2004). This protein shows a 23% sequence homology with the other 17-HSD isoenzymes, utilizes NAPDH as cofactor and it seems to be prevalently expressed in the fetal and adult testes. Extragonadal tissues such as bone, adipose tissue, sebaceous glands and brain have also been shown to express this enzyme

not determined fatty acid synthesis; 3-

CNS, kidney inactivates both E2 into

not determined enzymatically not

E 1 = Estrone; E2 = 17-estradiol; 5-diol = androst-5-ene 3 DHEA = dihydroepiandrosterone;

Table 1. The different types of identified 17-HSD with corresponding locations and

exception of the 17-HSD-2 which was not seen in peripheral blood (Hoppe et al., 2006). All 17-HSDs except 17HSD1 showed a significantly higher mRNA concentration in the foreskin compared to the scrotal tissue, demonstrating a tissue-specific local control of steroid hormone synthesis and action in addition to systemic effects (Hoppe et al., 2006). It has been demonstrated that the expression of 17-HSD5 increases with aging in scrotal skin fibroblasts and in peripheral blood mononuclear cells, while the 17-HSD3 mRNA expression is higher in the younger age subjects (Hammer et al., 2005; Hoppe et al., 2006). This implicates that 17-HSD3 has a more important role in childhood, which later is taken

It was also demonstrated the existence of a large inter individual variability of the enzymatic transcription patterns (Hoppe et al., 2006). Microarray investigation of multiple blood samples taken on different days from the same individual showed time-dependent differences in gene clustering. The nature and extent of inter individual and temporal variation in gene expression patterns in specific cells and tissues is an important and relatively unexplored issue in human biology (Whitney et al., 2003). In light of such intraand inter individual variability, basal and after stimulation levels of the steroid hormones

17-hydroxisteroid dehydrogenase type 3 (17-HSD3) isoenzyme catalyzes the reductive conversion of the inactive C-19 steroid, 4-A, into the biologically active androgen, T, in the Leydig cells of the testes (Payne § Hales, 2004). This protein shows a 23% sequence homology with the other 17-HSD isoenzymes, utilizes NAPDH as cofactor and it seems to be prevalently expressed in the fetal and adult testes. Extragonadal tissues such as bone, adipose tissue, sebaceous glands and brain have also been shown to express this enzyme

**Locations Functions Cofactor/** 

3, 17diol to androsterone; lipid metabolism

characterized

E1 and T into 4A; oxidation of FA

converts 5-androstane-

ketoacyl-CoA reductase

**reactions** 

NAD+/ oxidation

NADPH/ reduction

NAD+/ oxidation

not determine

d

**Gene location** 

4q22.1

11p11.2

4q22.1

19q13.33

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

17-HSD type 11 (HSD17B11)

17-HSD type 12 (HSD17B12)

17-HSD type 13 (HSD17B13)

17-HSD type 14 (HSD17B14)

FA = fatty acids

function

steroidogenic tissues, pancreas, liver, kidney, lung

NADPH/NADP+ = nicotinamide adenine di nucleotide phosphate;

4-A = androstenedione; T = testosterone;

over by the 17-HSD5 after puberty.

can vary a within wide range in normal subjects.

**2.3 17-hydroxisteroid dehydrogenase type 3** 

and heart

(Lukacik et al., 2006). It is encoded by *HSD17B3* gene which maps to chromosome 9q22; it is 60 kb in length and contains 11 exons. The cDNA encodes a protein of 310 amino-acids with a molecular mass of 34.5 kDa and no apparent membrane-spanning domain (Andersson et al., 1996).

It has been demonstrated that *HSD17B3* gene is constitutively suppressed and its transcription begins only upon removal of suppressors that act on the Alu repeat region located upstream of the translation site start of the gene promoter region (Xiaofei et al., 2006).

*HSD17B3* gene alterations affecting the enzyme function have been associated with a rare form of 46,XY disorder of sexual development (DSD), termed 17-hydroxisteroid dehydrogenase deficiency (Geissler et al., 1994).
