Inhibition of progesterone secretion and decrease of ovarian blood flow by isoxazole in pregnant rats

Pregnant rats were treated on day 11 of pregnancy with 0.62, 1.25, 2.5 or 5.0 mg of isoxazole per 100 g of body weight (bw) (Experiment I) or with 2.5 mg of isoxazole per 100 g of bw (Experiment II). In Experiment I animals were anaesthetized with pentobarbital at 48 hr. In experiment II animals were similarly anaesthetized at 0, 12, 24, or 48 hr following administration of isoxazole. Blood was collected separately from the ovary or from the uterus via a thin cannula which was inserted into the utero-ovarian vein. Blood was also collected from the vena cava inferior. The concentrations of progesterone (P), 17 beta-oestradiol (E2), and corticosterone were measured in blood samples by RIA. All of the animals exhibited reduced rates of ovarian venous blood flow and rates of P secretion when pregnancy was terminated by isoxazole (2.5 mg/100 g bw or greater). The concentration of P was found to be correspondingly reduced by 90% in ovarian venous blood and by 50% in peripheral blood, relative to the controls. After isoxazole had been administered, the rate of P secretion and also the concentration of P in peripheral blood continued to decrease rapidly and to remain at low levels for at least 48 hr. By contrast, the concentration of corticosterone in peripheral blood decreased during the first 12 hr but then it returned to the control levels by 48 hr. The ovarian secretion rate of E2 and the concentration of E2 in peripheral blood remained unchanged during the same 48 hr period.(ABSTRACT TRUNCATED AT 250 WORDS)