Blockade of pseudopregnancy in the rat by treatment with antiprogesterone serum.

Abstract

The role of peripheral progesterone in the initiation of pseudopregnancy (psp) was investigated. Antiprogesterone serum was generated in a rabbit immunized with progesterone-i lo-hemisuccinate coupled with ovine serum albumin and injected i.v. once or twice into cervically stimulated female rats. The uterine cervical stimulation was performed on proestrus (Day 0) at 1900 h. The antiserum was injected at various times between Days 0—2. Serum prolactin (PRL) and progesterone concen trations were determined by respective radioimmunoassays from Days 1 to 5. The amount of “?�free” progesterone was calculated by subtracting the amount of progesteronebound to the previ ously injected progesterone antibody from the total amount of progesterone. Injections of antiprogesterone serum (1 ml) at 0700 h on Days 1 and 2 prevented the initiation of psp in 9 of 10 rats, but the other combination of 2 injections was ineffective. In psp blocked rats, nocturnal surges of PRL decreased gradually in magnitude and were absent on Day 5, while diurnal surges were absent from Day 1. Free progesterone stayed at low levels between Days 3—5. Another group of rats received a single injection of antiprogesterone serum. Only the treatment at 0700 or 0800 h on Day 1 was effective in preventing the initiation of psp in 5 of 15 rats. Only those rats which underwent psp in spite of this treatment were used to measure changes in levels of free progesterone. Free progesterone concentrations were lowered on Days 2 and 3 and started to rise on Day 4 in contrast to normal psp rats whose first significant rise was observed on Day 3. The nocturnal surge was detectable throughout the period examined, but the magnitude on Day 2, 1 day after the antiprogesterone treatment, was suppressed. These results indicate that the magnitude of the nocturnal surge of PRL is attenuated if circu lating progesterone is curtailed at 0700 h of the previous morning and that the occurrence of the diurnal surge of PRL is highly susceptible to the level of peripheral progesterone. Antiprogesterone treatment at 0700 h on Day 1 or 2 will trigger the following sequential events: attenuation of the nocturnal surge, preclusion of the diurnal surge, impairment of progesterone secretion and, finally, interruption of psp.