Modulation of rat epididymal gamma-glutamyl transpeptidase by nonylphenols.

1. gamma-Glutamyl-transpeptidase (gamma-GTP), present at low levels in the testis, seminal vesicle, prostate gland and epididymis in rat at 4 days of age, showed rapid developmental increases at the time of weaning. 2. Administration of nonylphenols (NP) to the neonatal male rat pup (from days 1 to 15) impaired the subsequent development of gamma-GTP in the epididymis but not in the testis, seminal vesicles or prostate gland. 3. Single injection of NP to weaned pups at approximately 22 days of age decreased gamma-GTP in the epididymis but not in other male accessory sex organs. This effect was transient, dose-dependent and blocked by the oestrogen receptor-specific antagonist ICI 182,780. 4. Single injection of oestradiol to weaned rat at approximately 22 days of age also decreased gamma-GTP in the epididymis but not in the testis, prostate gland or seminal vesicles. 5. In in vitro assays, NP did not inhibit epididymal gamma-GTP activity even at 100 microM final concentration. Under similar conditions, acivicin, a specific inhibitor for gamma-GTP, showed a dose-dependent inhibition of gamma-GTP activity. 6. It is suggested that NP impair gamma-GTP expression in the epididymis of developing male rat and act in part via the oestrogen receptor.

Effect of neonatal hypoxia on the development of hepatic lipase in the rat.

Increases in plasma lipids occur during hypoxia in suckling but not in weaned rats and may result from altered hepatic enzyme activity. We exposed rats to 7 days of hypoxia from birth to 7 days of age (suckling) or from 28 to 35 days of age (weaned at day 21). Hypoxia led to an increase in hepatic lipid content in the suckling rat only. Hepatic lipase was decreased to approximately 45% of control in 7-day-old rats exposed to hypoxia but not in hypoxic 35-day-old rats. Hypoxic suckling rats also had a 50% reduction in lactate dehydrogenase activity, whereas transaminase activity and CYP1A and CYP3A protein content were not different between hypoxic and normoxic groups. Additional rats were studied 7 and 14 days after recovery from hypoxic exposure from birth to 7 days of age; hepatic lipase activity had recovered to 85% by 7 days and to 100% by 14 days in the rats previously exposed to hypoxia. Administration of dexamethasone to neonatal rats to simulate the hyperglucocorticoid state found in hypoxic 7-day-old rats led to a moderate decrease ( approximately 75% of control) in hepatic lipases. Developmentally, in the normoxic state, hepatic lipases increased rapidly after birth and reached levels more than twofold that of the newborn by 7 days of age. Hypoxia delays the maturation of hepatic lipases. We suggest that the decrease in hepatic lipase activity contributes to hyperlipemia in the hypoxic newborn rats.