Induction of Pseudopregnancy and Prolactin Surges by a Single Injection of Progesterone

Abstract

Pseudopregnancy (psp) was induced by progesterone injections during the estrous cycle in 4 day cycling rats kept under a lighting condition of 14L:10D (lights on 0500 h). When a single dose of 10 mg progesterone was injected s.c. at 0700 or 0800 h on the day of estrus (Day 1), rats responded with leukocytic vaginal smears. In these rats a pattern of progesterone secretion similar to that in cervically stimulated rats was obtained when the values of endogenous progesterone levels were estimated mathematically; it was assumed that the decreasing rate of the administered progesterone in circulation was not different between these rats and ovariectomized rats. Pentobarbital anesthesia before the progesterone injection prevented the induction of psp. In addition, the effectiveness of progesterone injected at 0700 h on Day 1 was severely reduced by giving an injection of the same amount of progesterone 1 or 2 h before. Progesterone injected at 0700 h on Day 1 caused a dramatic increase of serum prolactin (PRL) 1 h later and the level was maintained for at least 4 h. However, progesterone injected at 0400 h on Day 1 induced neither psp nor an elevation of PRL. In the rats treated at 0700 h on Day 1, the second elevation of serum PRL appeared at 0500 h on Day 3 and coincided chronologically with the nocturnal surges found in normal psp rats; typical twice daily PRL surges were then established from Day 4. An additional injection of progesterone 1 day after the first injection at 0700 or 1800 h on Day 2 completely inhibited the establishment of psp. These results suggest that two requirements must be fulfilled for the induction of psp by a single injection of progesterone: 1) the injection should be done at a special time (at 0700 or 0800 h on Day 1); 2) a rapid increase in PRL secretion should be brought about. The mechanism through which progesterone induces psp is probably through the hypothalamo-hypophysial axis which controls PRL secretion either in a facilitative or inhibitory way according to the time of progesterone injection.