A novel pathway for progestin receptor activation that influences both neuronal response and behavior in female rats

Ovarian steroid hormones influence both behavior and physiology in a variety of species by binding to intracellular steroid receptors. Recent studies suggest that steroid receptors (e.g., estrogen and progestin receptors) may also be activated in the absence of steroid. Infusion of dopamine agonists into the third ventricle of estradiol-primed female rats can increase estrous behavior, and this increase can be blocked by prior treatment with progestin antagonists even in the absence of progesterone. However, it is not known if progestin receptors in rat brain are activated in the absence of circulating progesterone under physiological conditions affecting neuronal responses and behavior. This dissertation attempts to determine if somatosensory cues that are normally experienced by females, such as stimuli associated with sexual contact with males, activate progestin receptors to influence both neuronal response and estrous behavior in the absence of circulating progesterone. Using immunocytochemistry, it is possible to determine the expression of immediate early gene products that suggest neuronal response to particular stimuli. It was found that either progesterone or stimuli associated with mating can increase immunostaining of the immediate early gene product, Fos, within cells that contain progestin receptors. Thus, some neurons in female rat brain are capable of integrating somatosensory information provided by the male and information relating to serum progesterone levels. In addition, increases in Fos expression in female rat brain following stimuli associated with mating can be blocked by prior treatment with progestin antagonists even in the absence of circulating progesterone. This suggests that the response of some neurons to mating-related stimuli are mediated via progestin receptors. It was also found that a component of estrous behavior (e.g., lordosis) in female rats can be facilitated by repeated exposure to males in the absence of progesterone, and this facilitation can be blocked by prior treatment with progestin antagonists. The present results suggest that progestin receptors in some neurons in rat brain are activated by mating related stimuli in a progesterone-independent manner. These data suggest a pathway by which mating-related stimuli or other environmental influences could activate steroid receptors influencing neuronal response and behavior in the absence of circulating progesterone