Prenatal exposure to dexamethasone alters Leydig cell steroidogenic capacity in immature and adult rats

This study examines the effects of prenatal exposure to dexamethasone (DEX) on postnatal testosterone production in male rats. Pregnant female rats we re treated on gestation days 14-19 with DEX (100 mug/kg body weight per day ; n = 9) or vehicle (n = 9). Results show that 35-day-old male offspring fr om DEX-treated pregnant females (n = 42) had decreased levels of serum test osterone (45.6% lower, P < .05) compared with control offspring (n = 43), a lthough serum luteinizing hormone (LH) levels were not significantly altere d. These findings suggest that a direct programming of developing gonadal c ells occurs in response to high levels of maternal glucocorticoid. Indeed, testosterone production was significantly reduced in Leydig cells isolated from immature offspring of DEX-treated pregnant females compared with contr ols (48.3%, P < .001), and LH stimulation of these cells did not compensate for the lowered steroidogenic capacity. The hypothalamic-pituitary-adrenal axis was also affected, because significant reductions in both serum adren ocorticotropic hormone (ACTH; 26.2%, P < .001) and corticosterone (CORT; 32 .3%, P < .001) were measured in DEX-exposed immature male offspring. In con trast, adult male offspring from DEX-treated dams had significantly higher levels of serum ACTH (39.2%, P < .001) and CORT (37.8%, P < .001). These sa me animals had higher serum testosterone (31.6%, P less than or equal to .0 5) and a significant reduction in serum LH (30.8%, P < .001). Moreover, Ley dig cells isolated from these adult offspring exhibited an increased capaci ty for testosterone biosynthesis under basal (38.6%, P < .001) and LH-stimu lated conditions (33.5%, P < .001). In summary, sustained changes in steroi dogenic capacity were observed in male rats exposed to high levels of gluco corticoid during prenatal development. More specifically, DEX exposure, in utero perturbed Leydig cell testosterone production in both pubertal and ad ult rats.