Behavioral effects of progestin in the brain.

In this article we review research on the role of progestins in the regulation of estrous responsiveness in female rats. Estrous responsiveness normally results from a synergistic action of estradiol (E2) and progesterone (P). E2 primes the system but normally does not result in estrous behavior. The full expression of estrous responsiveness results from the action of P on the E2-primed system. It has been demonstrated with implants of dilute E2 (1 part E2: 250 parts cholesterol) that the site of E2 priming is the ventromedial nucleus of the hypothalamus (VMN). In females primed with systemically administered E2, P also acts on the VMN to facilitate full estrous responsiveness. It has been shown in addition that estrous responsiveness results from sequential application of E2 and P to the VMN but not to other areas of the brain. The VMN is also the site at which P produces sequential inhibition of estrous responsiveness. The time course of P action in facilitating full estrous responsiveness is about two hours, regardless of whether the hormone is administered intracerebrally or intravenously. The duration of estrous responsiveness is directly correlated with the length of time P is in contact with brain tissue. Experiments with the protein synthesis inhibitor anisomycin are consistent with the view that P acts in the VMN by way of a protein synthetic mechanism to facilitate estrous behavior; however, other mechanisms must be considered as alternatives. Finally, we address the question of whether estrogenic priming depends upon induction of progestin receptors in the VMN. Results indicate that estrogenic priming of estrous responsiveness may occur without concomitant induction of progestin receptors.