Progestins and antiprogestins are widely used therapeutic agents in humans. In many cases, these are indicated for the treatment of reproductive activities. However,
progesterone has widespread physiological effects including a reduction of the response to stress. We have reported that 5 min of restraint reduced
lordosis behavior of ovariectomized rats hormonally primed with
estradiol benzoate. When ovariectomized rats received both
estradiol benzoate and
progesterone priming, restraint had minimal effects on
lordosis.
Progesterone influences behavior through classical intracellular
progesterone receptor-mediated nuclear events as well as extranuclear events. How these multiple events contribute to the response to stress is unclear. The current project was designed to initiate examination of the mechanisms responsible for
progesterone's ability to protect against the effects of the restraint. In the first experiment, ovariectomized rats, primed with 10 μg
estradiol benzoate, received 500 μg
progesterone 4 h, 1 h, or 30 min before restraint. When
progesterone was injected 4h before restraint,
progesterone eliminated the effects of restraint. In contrast,
progesterone 30 min before restraint offered no protection. Effects of
progesterone 1h before restraint were equivocal allowing the suggestion that less than 4h of
progesterone priming might be sufficient. In the second experiment, the
synthetic progestin,
medroxyprogesterone, was shown to mimic effects of
progesterone in preventing effects of restraint. Finally, the
progesterone receptor antagonist,
RU486, attenuated
progesterone's protection against restraint. These findings offer evidence that
ligand-activated
progesterone receptor mechanisms contribute to the maintenance of
lordosis behavior in the presence of mild stress.