**4. Regulation of HSDs function**

270 Dehydrogenases

Differentiation of progenitors to newly formed adult Leydig cell is associated with the cell cytoplasm shape change from spindle shaped to polygonal. Newly formed Leydig cells move toward the central interstitium and locate near blood capillaries although they do not exclusively arrange in clusters. These cells express LHR and the levels of 3β–HSD VI, P450scc and P450c17 increase with the further steps of Leydig cell differentiation (Ariyaratne & Mendis-Handagama, 2000; Shan et al., 1993). It has been demonstrated that in mice *Hsd3b3* and *Hsd3b6,* remain fairly stable after birth but show a pubertal rise in

5α-androstane-3α and 17β-diol is synthesized as the predominant androgen with the emergent increase in activity of 17β–HSD 3 and in a continuous presence of 5α-reductase and 3α-HSD (Hardy et al., 1990). It is worth noting, that in immature ALCs 11βhydroxysteroid dehydrogenase type 1 (11β-HSD 1) and 11β-hydroxysteroid dehydrogenase type 2 start to be expressed. In the rat testis, the presence of 11β-HSD 1 is in coincidence with the first appearance of elongated spermatids in the seminiferous tubules (Haider, 2004).

Adult Leydig cells are the dominant cell type of the Leydig cell lineage from pd 56 (Benton et al., 1995). Transformation of immature adult Leydig cells into mature adult Leydig cells is characterized by a significant increase in the average cell size and disappearance of cytoplasmic lipid droplets. The capacity to secrete T increases significantly in mature adult Leydig cells because of their enhanced responsiveness to circulatory LH due to the acquisition of higher numbers of LHR. During this time in the mouse testis, 3β-HSD VI

Additionally, the sharp decline in 5α-reductase activity overlaps. Shan et al. (1993) have reported that the mature Leydig cells by pd 90 produce 150 times more T than progenitors, and five times more than immature Leydig cells. Such high T levels are required for initiation, maintenance and regulation of the spermatogenesis. By day 90 the secretory

During puberty ALCs are particularly sensitive to androgens and expression of AR mRNA in this time is significant. Studies have shown that in the absence of AR, there is developmental failure of ALC maturation (O'Shaughnessy et al., 2010). However, there is well known phenomenon when ALCs destroyed by ethane dimethane sulphonate (EDS) administration can proliferate to regenerate the original population of Leydig cells (Teerds

In aging human testis, both serum and intratesticular T concentrations progressively decline being in correlation to decreased LH level. In rat, these changes have been reported to be strain-dependent (Harman et al., 2001). In Brown Norway rats, the decrease in T level concomitantly with an increase in FSH level and unchanged LH level have been detected (Chen et al., 2002). Several studies have demonstrated that in men decrease in T level is associated with alterations in body composition, diminished energy, muscle strength and physical function, depressed mood and decreased cognitive function (Matsumoto, 2002). These age related changes result from the loss of steroidogenic capacity of the Leydig cells and/or reduction in their number (Chen et al., 2001, 2009). It has also been found that in

expression around pd 20 (O'Shaughnessy et al., 2002)

becomes the predominant isoform of HSDs (Payne & Hales, 2004).

capacity per ALC in rat has been estimated as 1.43 pg.

& Rijnities, 2007).
