**4.4. Photopheriod**

272 Dehydrogenases

**4.2. Steroids**

P4 influences HSDs.

own studies have revealed that in bank voles treated with PRL, the levels of androgens and estrogens have increased markedly within the testis (Gancarczyk et al., 2006). These results point the role of PRL in promoting multiplication, differentiation and regulation of steroidogenic function of Leydig cells. Similar functions have been confirmed for thyroid hormones. In physiological levels these hormones have profoundly increased the number of mesenchymal precursors of ALCs and supported their further differentiation (Maran, 2003;

In Leydig cells, the action of P4, has been reported to be mediated only by non-classical receptors while the classical nuclear progesterone receptor has not been found in these cells (Oettel & Mucopadhay 2004). The direct stimulatory or inhibitory effect of P4 on steroidogenesis in Leydig cells has been demonstrated, although its mode of action remains obscure (El-Hefnawy et al., 2000; Schwarzenbach et al., 2003). In rats, exposure in utero to subnormal levels of hydroxyprogesterone suppresses testicular steroidogenesis by decreasing the HSDs levels, which in turn suppresses the reproductive activity of the male (Pushpalatha et al., 2003). Studies have shown that in elderly men P4 levels increase within the testis and the spermatic vein, having a detrimental effect on Leydig cell steroidogenic function (El-Hefnawy & Huhtaniemi, 1998). It is interesting but still not resolved if and how

It has been reported that both endogenous and exogenous sex hormones are able to modify steroidogenesis at the level of 3β-HSD. In rats treated with an androgen antagonist, increased induction of hCG and 3β-HSD activity has been observed, whereas treatment with an androgen agonist decreased hCG induction and 3β-HSD activity, respectively (Ruiz de Galarreta et al., 1983). Similarly, T and DHT have inhibited 3β-HSD activity in adult rat and mouse Leydig cells (Simard et al., 2005). Recent findings by Kostic at al. (2011) have demonstrated that in andorgenized rats, T upregulated P4 synthesis. In these animals prolonged treatment with high T doses caused significant increase of 3β-HSD mRNA and protein levels whereas no effect has been observed on 17β-HSD expression. Freeman (1985) has demonstrated that E2 inhibited P4 biosynthesis in a dose-dependent manner in Leydig cells via inhibition of the activity of 3β-HSD. Also studies *in vivo* on rats and bank voles treated with E2 have shown disturbances in sex hormones balance within the testis. Low T and high E2 levels in treated animals have been reported to affect spermatogenesis

It has already been accepted that the function and activity of the testis is regulated by many locally produced factors and by cell-cell interactions. The effects of cytokines and growth factors on HSDs expression has been reported to be diverse (for review see Herrmann et al., 2002). Tumor necrosis factor (TNF) and interleukin 1 (IL-1) inhibited 3β-HSD activity in mouse and rat Leydig cells. However, IL-1 only inhibited cAMP stimulated enzyme

Mendis-Handagama et al., 1998; Teerds et al., 1998).

(Gancarczyk et al., 2004; Rao & Chinoy, 1986).

**4.3. Testicular paracrine factors**

In seasonal breeders the function of the pituitary-testicular axis undergoes annual cyclic variations. Multiple studies including our own have shown that photoperiod is an important factor regulating steroidogenesis. Changes in LH and FSH secretion depending on the light length are responsible for seasonal variations in size, structure and function of the testis (Bartke & Steger, 1992). Under laboratory conditions, bank voles kept in long light regime show higher testis weight and increased steroidogenic activity than animals exposed to short one (Bilinska et al., 2000, 2001; Tähkä et al., 1982). In several seasonal breeders, the serum and testicular concentrations of steroid hormones have exhibited seasonal fluctuations and are always lower in regressed animals (Frungieri et al., 1999; Hance et al., 2009; Kotula-Balak et al., 2003).

In addition, the Leydig cell morphology as well as localization and expression of HSDs have been found to change seasonally in the sika deer, black bear and northern fur seal (Hayakawa et al., 2010; Ibluchi et al., 2010; Tsubota et al., 1997, 2001). In black bears during their mating season, 17β-HSD 3 has been detected both in Leydig cells and in Sertoli cells. Moreover, in these animals expression of 3β-HSD was the highest in June. In Syrian hamster, specific melatonin receptors (mel1a) have been reported in Leydig cells via which melatonin down-regulated the gene expression of both 3β-HSD, and 17β-HSD (Frungieri et al., 2005).
