Intrahypothalamic injection of RU486 antagonizes the lordosis induced by ring A-reduced progestins

We explored the possibility that ring A-reduced progestins facilitate lordosis in estrogen primed rats through their interaction with an intracellular progestin receptor (PR) by using RU486. This drug binds with high affinity to the PR, thus preventing the action of progesterone (P). Ovariectomized estrogen-primed rats (2 micrograms estradiol benzoate 40 hr earlier) were bilaterally injected into the ventromedial hypothalamic nucleus (VMHN) with 1 microgram of: P, 5 alpha-pregnanedione or 3 beta,5 beta-pregnanolone in 1 microliter oil. All three progestins effectively facilitated lordosis, tested at four and eight hours after intrahypothalamic injections. The ability of RU486 to counteract progestin-induced lordosis was assessed by infusing 10 micrograms of this agent into the VMHN along with any of the progestins. RU486 antagonized the lordosis induced not only by P (67% reduction) but also that induced by 5 alpha-pregnanedione and by 3 beta,5 beta-pregnanolone (47% and 93% reductions, respectively). Results suggest that ring A-reduced progestins may act through the PR mechanism to facilitate lordosis, i.e., in a fashion similar to P.