Failure of high uterine concentrations of progesterone to inhibit myometrial activity in vivo in the post-partum rat.

In a pilot experiment to test the feasibility of studying the progesterone 'block' in a species other than the rabbit, it was found that the myometrial activity of the post-partum rat recorded in vivo by means of small indwelling recording balloons was not reduced following intramuscular injections of progesterone (10 mg in oil). In view of the ample evidence that progesterone is essential in maintaining pregnancy in the rat after ovariectomy (Johnson & Challans, 1930; Rothchild & Meyer, 1940), this paradoxical finding was investigated in more detail. On the day following parturition, six Holtzman rats were anaesthetized with tribromoethanol intraperitoneally and a small latex recording balloon attached to a polyethylene catheter (0\m=.\015 in. i.d. \m=x\0\m=.\043in. o.d.) was placed in one uterine horn through a mid-line incision made with antisepsis precautions. The ovaries were removed and the catheter was passed subcutaneously to a point at the back of the neck where it was brought to the exterior. On the day of surgery, the animals were injected subcutaneously with 5 \g=m\g oestradiol-17\g=b\. Three further injections of 0\m=.\5 \g=m\g were given daily, beginning 3 to 7 days later. On the last day, the animals received in addition a subcutaneous injection of 25 mg progesterone (crystalline suspension, Upjohn) over the spine (to prevent contamination of the uterus when it was removed subsequently). Intrauterine pressure was monitored continuously from the virtually unrestrained conscious rats by means of Statham pressure transducers and a Grass 7B polygraph. The animals were killed 24 hr after the progesterone treatment. Blood samples were taken from the carotid artery into heparinized tubes, centrifuged imme¬ diately at 4°C and the plasma was stored at — 20CC until analysis. Portions of uterine tissue were removed and frozen immediately. Progesterone was measured in samples of plasma and uterine tissue by radioimmunoassay. The methods used have been described and validated elsewhere (Challis, Davies & Ryan, 1973). Spontaneous myometrial activity was not diminished in any of the six rats during the 24 hr after the progesterone treatment (Text-figs 1 and 2). Although the maximum amplitude during this period remained at around 34 mmHg,