Effect of acute and chronic estrone, estradiol, and estriol treatment on hepatic, pulmonary, and intestinal mixed-function mono-oxygenase activities in female rats

The effects of acutely and chronically administered estrone (E₁), estradiol (E₂) and estriol (E₃) on microsomal aryl and hydrocarbon hydroxylase (AHH) activity, 7-ethoxycoumarin O-de-ethylase (ECD) activity, and cytochrome P-450 content in rat liver, lung and intestinal mucosa were compared. Forty-day-old Sprague-Dawley female rats were given 1.0 mg of E₁, E₂, or E₃ per kg ip, twice daily for 2 days in acute studies, and once daily for 7 days in chronic studies. Acute treatment with E₁, E₂, and E₃ resulted in significant increases in hepatic and intestinal AHH activities, and hepatic cytochrome P-450 content. Acute treatment of female rats with the three estrogens had no effect on hepatic, pulmonary, and intestinal ECD activities. After acute treatment, the AHH activity of lung microsomes increased approximately 2-fold with E₃, remained unchanged with E₁, and exhibited a decrease with E₂. Acute treatment with E₁, E₂ and E₃ produced no changes in pulmonary ECD activity. Chronic treatment of the animals with E₃ resulted in a significant increase in intestinal AHH activity, but no changes in the AHH of ECD activities of lungs or liver. Chronic treatment with E₁ and E₂ produced increased activities of liver and intestinal AHH and ECD, and increased hepatic cytochrome P-450 content. Both chronic E₁ and E₂ significantly decreased lung microsomal AHH and ECD activities. A time-course study with E₃ demonstrated that maximum activity of AHH in lungs and liver occurred after 2 days of treatment and decreased thereafter, returning to normal by day 3. These data indicate that in the female rat the inducibility of AHH and ECD activities are organ-specific and depend upon the estrogen administered as well as the duration of steroid treatment. The difference observed may be explained on the basis of estrogen receptors.