Effects of oxytocin and uterine and luteal prostaglandins on the functional regression of the corpus luteum in pseudopregnant rats.

The effects of oxytocin on luteal regression in the pseudopregnant rat and whether the luteolytic effect of oxytocin could be blocked by an oxytocin receptor antagonist were investigated. We determined the temporal relationship between the effects of oxytocin on the duration of pseudopregnancy and concentrations of progesterone in plasma, and uterine and luteal prostaglandin concentrations. Pseudopregnancy was induced in normal cyclic rats by gonadotrophin treatment. On day 6 of pseudopregnancy, rats were assigned to one of three groups. One group was given oxytocin, 500 mU s.c., twice a day for three days. A control group was given saline injections. A third group was given the same dose of oxytocin and an oxytocin receptor antagonist, [Pen1,Phe(Me)2,Thr4,Orn8]oxytocin, 300 micrograms day-1, delivered by micro-osmotic pumps for the same three-day period. Rats were either observed to determine the duration of pseudopregnancy, or killed on days 2, 6, 7, 9, 11 and 13 of pseudopregnancy for measurements of plasma concentrations of progesterone and luteal and uterine PGF2 alpha and PGE2 concentrations by radioimmunoassays. Oxytocin injections shortened the duration of pseudopregnancy from the mean of 13.5 +/- 0.3 days for the control group to 11.5 +/- 0.3 days for the oxytocin-treated group (P < 0.01). The oxytocin-induced shortening of pseudopregnancy was associated with a premature functional regression of the corpus luteum. Both luteal and uterine PGF2 alpha concentrations were found to increase with luteolysis and reached peak values before the return of oestrus. However, only uterine PGF2 alpha synthesis was stimulated by oxytocin treatment. There was no significant increase in uterine or luteal PGE2 synthesis during luteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)