Steroidogenic enzyme activity in the rat testis following Leydig cell destruction by ethylene-1,2-dimethanesulphonate and during subsequent Leydig cell regeneration

Abstract

ABSTRACT Ethylene-1,2-dimethanesulphonate (EDS) rapidly destroys Leydig cells in the rat testis, although repopulation occurs within 5–7 weeks. In this study we have examined the activity of testicular steroidogenic enzymes after Leydig cell destruction and during regeneration. This was designed to measure the contribution of cells, other than Leydig cells, to steroidogenic activity in the testis, and to determine whether changes in steroidogenic enzyme activity during Leydig cell regeneration after EDS parallel those which occur during normal Leydig cell development. The enzymes studied are those responsible for androgen synthesis and metabolism in the testis. Adult male Wistar rats (300–350 g) were injected with EDS (100 mg/kg, i.p.) and testicular steroidogenic enzyme activity was measured on days 0, 3, 7, 14, 21 and 35. On day 3, when no Leydig cells remain in the testis, cholesterol side-chain cleavage (CSCC) activity, per testis, declined to undetectable levels, while 3βhydroxysteroid dehydrogenase (3βHSD) and 17α-hydroxylase retained only 0·04 and 0·15% of control activity respectively. In contrast, 17-ketosteroid reductase (17-KSR) and 5α-reductase retained 33 and 10% of control activity respectively. On day 7 there was a further loss of 17-KSR activity (to 20% of control) but no change in other enzymes. The 17-KSR activity remaining on day 7 after EDS was contained almost exclusively in the seminiferous tubules, while the low 3β-HSD activity remaining was confined largely to the interstitial tissue. Other enzymes showed a more even distribution between the two compartments. On day 14 after EDS there was a tenfold increase in 3β-HSD activity (compared with day 7), with no change in CSCC, 17α-hydroxylase or 5α-reductase and a further loss of 17-KSR (to 11% of control). Between days 14 and 21 there were marked increases in the activities of CSCC, 3β-HSD, and 17α-hydroxylase, while 17-KSR showed no change in activity from day 14. Activity of 5α-reductase increased between days 14 and 21 to levels greater than those seen in control animals. By day 35 the activities of all enzymes had returned to control levels. The results show that, in the adult rat testis, the activities of CSCC, 3β-HSD and 17α-hydroxylase are confined, almost entirely, to the Leydig cells, and only 17-KSR shows significant activity in another cell type. During regeneration of Leydig cells after EDS the pattern of changes in enzyme activity is very similar to that seen in the normal development of the adult population of Leydig cells. Journal of Endocrinology (1991) 131, 451–457