Effect of Chronic Phenobarbital Treatment on the Liver Microsomal Metabolism and Uterotropic Action of 17β-Estradiol1

Abstract
Treatment of immature female rats with phenobarbital (37 mg/kg, intraperitoneally, twice daily) for 3 days increases the activity of liver microsomal enzymes that metabolize 17[beta]-estradiol. The stimulatory effect of chronic phenobarbital administration on in vitro estradiol metabolism is paralleled in vivo by a blockade in the estradiol-induced increase in uterine wet weight and the incorporation of glycine-Cl4 into uterine protein. However, a single dose of phenobarbital (45 mg/kg, intraperitoneally), given 1 hr before the estrogen, does not inhibit estradiol-induced increases in uterine wet weight. The inhibitory action of chronic phenobarbital treatment on the increase in uterine wet weight caused by estradiol is not prevented by adrenalectomy or hypophysectomy, indicating that phenobarbital does not act through the pituitary-adrenal axis.