Concentrations of cholecystokinin, substance P, and bombesin in discrete regions of male and female rat brain: sex differences and estrogen effects.

The distributions of cholecystokinin, substance P, and bombesin was measured in discrete regions of the hypothalamus and limbic system in male and female rats. Higher levels of cholecystokinin immunoreactivity were determined for males compared with females during the estrous cycle in the posterior-medial aspect of the amygdaloid complex, bed nucleus of the stria terminalis, medial preoptic area, paraventricular nucleus, and ventromedial nucleus. The only region that always contained greater substance P immunoreactivity in the male was the posterior-medial amygdala. No sex differences were observed for the levels of bombesin immunoreactivity. During the estrous cycle, significantly lower levels of cholecystokinin immunoreactivity occurred during the morning of estrus in the posterior-medial amygdala, bed nucleus, median eminence, and ventromedial nucleus, whereas substance P immunoreactivity was lower on estrus in the bed nucleus and ventromedial nucleus. In the posterior-lateral aspect of the amygdala, females were observed to have more cholecystokinin immunoreactivity than males although no significant variations occurred during the estrous cycle. Bombesin-immunoreactive levels were unchanged throughout the estrous cycle in all regions assayed. In a separate experiment to test the hypothesis that estradiol enhances the release of cholecystokinin from terminals in the mediobasal hypothalamus, this region was dissected from ovariectomized and ovariectomized estrogen-primed rats and superfused with estradiol-17 beta. Indeed, exposure of the tissue to estradiol-17 beta was observed to enhance the K+-stimulated release of cholecystokinin from a mediobasal hypothalamic block in vitro. These results, as well as the variation of cholecystokinin during the estrous cycle, imply an important role for cholecystokinin in the regulation of steroid-initiated reproductive events.