Comparative potency of several progestogenic compounds in a battery of different biological tests.

Abstract

This report compares the effectiveness of various compounds with progestogenic activity in a series of tests involving the chick the rat the mouse and the rabbit. The inhibition of oviduct growth stimulation of decidual growth and the Clauberg test were used for measurement of activity of 17-alpha-hydroxyprogesterone 17-alpha-hydroxyprogesterone caproate 11 dehydroprogesterone 17-alpha-ethyl-19-nortestosterone and 17-alpha-ethinyl-19-nortestosterone. In the chick oviduct test 16-day-old female white Leghorns were treated for 7 days and sacrificed on Day 8. The entire genital tract from the infundibulum to the cloaca was included in the oviduct weight. Injection of stilbestrol alone gave a typical sigmoid dose-response curve with a sharp increase in weight from 13 mg % of body weight at .05 mg daily to 1048 mg percent at 1 mg daily. A standard dose of 1 mg a day of stilbestrol was then selected for further experiments. Progesterone produced a marked inhibition of the stilbestrol-stimulated oviduct in the chick particularly when dissolved in oil; all the compounds tested showed some inhibition ability. Adult female Holtzman rats were castrated treated with 1 mg of estrone for 4 days followed by 9 days of progesterone or one of the test compounds. The uterus was exposed on Day 5 of test-drug treatment and 1 mg of histamine dihydrochloride injected into the left horn. A marked deciduoma was apparent with .5 mg progesterone daily. The degree of deciduomatogenesis was evaluated by comparing the percentage of increase of the histamine-treated horn with the other. At .2-2 mg daily progesterone gave a good dose response curve up to 400% increase when suspended in oil. Suspension of the hormone in saline with "Tween 80" decreased activity by 50%. 11-dehydroprogesterone was twice as effective as progesterone. The other compounds gave little or no response even in large doses. In mice similar tests showed the decidual response in the mouse is a more sensitive index of progestone-like activity than in the rat. No significant activity was observed with any of the test compounds except 17-alpha-ethyl-19-norethisterone. The Clauberg test in rabbits gave similar results to previously reported work. 11-dehydroprogesterone was effective at .15 mg twice the activity of progesterone. It had only a third the activity of progesterone in the Hooker-Forbes test. Both the 17-alpha-ethyl-19-nortestosterone and the 17-alpha-ethinyl-19-nortestosterone appeared to be superior to progesterone in Clauberg and chick-oviduct tests; the ethynyl derivative was superior to the ethyl derviative in the chick test; only 11-dehydroprogesterone mirrored all the activities of progesterone and was consistently superior to the hormone.