Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate

Exposure of rodents to phthalates is associated with developmental and repr oductive anomalies, and there is concern that these compounds may be causin g adverse effects on human reproductive health. Testosterone (T), secreted almost exclusively by Leydig cells in the testis, is the primary steroid ho rmone that maintains male fertility. Leydig cell T biosynthesis is regulate d by the pituitary gonadotropin LH. Herein, experiments were conducted to i nvestigate the ability of di(2-ethylhexyl)phthalate (DEHP) to affect Leydig cell androgen biosynthesis. Pregnant dams were gavaged with 100 mg(-1) kg( -1) day(-1) DEHP from Gestation Days 12 to 21. Serum T and LH levels were s ignificantly reduced in male offspring, compared to control, at 21 and 35 d ays of age. However, these inhibitory effects were no longer apparent at 90 days. In a second set of experiments, prepubertal rats, from 21 or 35 days of age, were gavaged with 0, 1, 10, 100, or 200 mg(-1) kg(-1) day(-1) DEHP for 14 days. This exposure paradigm affected Leydig cell steroidogenesis. For example, exposure of rats to 200 mg(-1) kg(-1) day(-1) DEHP caused a 77 % decrease in the activity of the steroidogenic enzyme 17 beta -hydroxyster oid dehydrogenase, and reduced Leydig cell T production to 50% of control. Paradoxically, extending the period of DEHP exposure to 28 days (Postnatal Days 21-48) resulted in significant increases in Leydig cell T production c apacity and in serum LH levels. The no-observed-effect-level and lowest-obs erved-effect-level were determined to be 1 mg(-1) kg(-1) day(-1) and 10 mg( -1) kg-1 day(-1), respectively. In contrast to observations in prepubertal rats, exposure of young adult rats by gavage to 0, 1, 10, 100, or 200 mg(-1 ) kg(-1) day(-1) DEHP for 28 days (Postnatal Days 62-89) induced no detecta ble changes in androgen biosynthesis. in conclusion, data from this study s how that DEHP effects on Leydig cell steroidogenesis are influenced by the stage of development at exposure and may occur through modulation of T-bios ynthetic enzyme activity and serum LH levels.