**5. HSDs in pathological conditions**

274 Dehydrogenases

the cytoplasm (Figure 3).

(arrowhead). Bars 20 µm.

Our recent results have shown that administration of the estrogenic compound, 4-*tert*octylphenol (OP), to adult bank voles has caused the significant decrease of 3β-HSD and increase of P450arom expression concominantly with the alteration of the androgen/estrogen balance within the tesis of sexually active animals (Hejmej et al,. 2011b). Similar results have been reported by Victor-Costa et al. (2010) on rats treated with atriazine. These authors concluded that inhibition of 3β-HSD function is one of the possible mechanism through which xenoestrogens disturb spermatogenesis. *In vitro* studies on Leydig cells obtained from various mammals have revealed decrease in the activity and expression of 3β-HSD after OP, bisphenol A (BPA) and genistein administration (Hu et al., 2010; Kotula-Balak et al., 2011; Ye et al., 2011). Our study demonstrated that OP markedly disturbes morphology and steroidogenic function of the Leydig cells through direct effect on 3β-HSD expression and localization (Kotula-Balak et al., 2011). In detail, treatment with high doses of OP (10-4–10-6 M) resulted in a reduced staining intensity and the staining was usually located near the nucleus, whereas in the low OP doses (10-7 and 10-8 M) it was manly dispersed throughout

**Figure 3.** (A-C) Immunostaining for 3β-HSD. Positive staining of various intensity is confined to the cytoplasm of Leydig cells (arrows). Note, clearly reduced staining for 3β-HSD in Leydig cells treated with high OP dose (B). In many cells weak to moderate staining in the perinuclear region is visible (arrowheads). In Leydig cells treated with low OP dose (C) the intensity of immunostaining is similar to

It is worth noting that the effect of EDCs on HSDs function can be diverse depending on the choice of animal species, age, routes of administration and dose levels. Studies of Pogrmic-Majkic et al. (2010) have shown that in rat Leydig cells atriazine stimulated 17β-HSD, whereas other authors reported inhibition of these enzyme in rat and human microsomes treated with various xenoestrogens (Hu et al., 2010; Vaithinathan et al., 2008; Ye et al., 2011). Recently, it has also been found that antiandrogens such as tributylin, triclosan and flutamide modified HSDs expression in Leydig cells and microsomes of various mammals (Kim et al.,

that of the control (A), (arrows). Only in a few cells staining in the perinuclear region is visible

2008; Kumar et al., 2009; McVey & Cooke, 2003; Ohno et al., 2005; Ohsako et al., 2003).
