Facilitation Of Estrous Behavior Research Articles

Src kinase signaling mediates estrous behavior induced by 5β-reduced progestins, GnRH, prostaglandin E2 and vaginocervical stimulation in estrogen-primed rats

The progesterone receptor (PR) is a dual function protein that acts in the nucleus as a transcriptional factor and at the cytoplasm as a scaffold for the Src–MAPK signaling pathway. Several agents lacking affinity for the PR, such as 5β-reduced progestins, GnRH or prostaglandin E2 (PGE2) facilitate estrous behavior in ovariectomized (ovx), estrogen-primed rats yet their action is blocked by the antiprogestin RU486. We hypothesize that these agents act by using the PR–Src–mitogen activated protein kinase alternative pathway. To test this hypothesis we used PP2, a specific inhibitor of the Src kinase family. Intraventricular infusion of 30μg of PP2, 30min before behavioral testing, significantly attenuated estrous behaviors induced in estradiol benzoate (E2B)-primed rats by 5β-dihydroprogesterone (5β-DHP), 5β-pregnan-3β-ol-20-one (5β,3β-Pgl), GnRH, PGE2 and by manual flank/vaginocervical stimulation. These results suggest that the Src signaling system, by activating mitogen-activated protein kinases, participates in the facilitation of estrous behavior in E2B-primed rats induced by agents lacking affinity for the PR.

Differential effects of progesterone and genital stimulation on sequential inhibition of estrous behavior and progesterone receptor expression in the rat brain

The effect of genital stimulation, either by vaginocervical stimulation (VCS) using a calibrated vaginal probe combined with manual flank stimulation (FS), or by mounts performed by the male, on the hypothalamus and preoptic area concentration of the progesterone receptors A (PR-A) and B (PR-B) was assessed in ovariectomized (ovx) estrogen-primed rats. VCS/FS or stimulation provided by male mounts, even without intromission, significantly decreased PR-B concentration in the hypoythalamus. Down regulation of PR produced by genital stimulation was quantitatively similar to that elicited by progesterone (P) administration. Bilateral or unilateral transection of the pelvic or the pudendal nerves prevented down regulation elicited by VCS/FS. Repeated VCS/FS elicited lordosis behavior in most ovx estrogen primed rats, but the lordosis intensity was lower than that observed in response to P. P administered to ovx estrogen primed rats, induced sequential inhibition, i.e., failure to display estrous behavior in response to a second P injection (24 h after the initial P injection). VCS/FS failed to elicit sequential inhibition, since rats responded with normal estrous behavior to the second injection of P. This suggests that down regulation by VCS, by contrast with P, failed to inhibit the subpopulation of PR involved in the facilitation of estrous behavior by P.

Actions of RU 38486 on progesterone facilitation and sequential inhibition of rat estrous behavior: Correlation with neural progestin receptor levels

The present study examined the actions of the antiprogestin RU 38486 on progesterone (P)-induced facilitation and sequential inhibition of estrous behavior and on brain cytosol progestin receptor (PR) levels in ovariectomized, estrogen-primed (0.5 μg of estradiol benzoate for 3 days) female rats. RU 38486 suppressed P-facilitated receptive and proceptive responses in a dose-dependent fashion when administered 1 hr prior to P. RU 38486 did not, however, block the sequential inhibitory effect of P. Indeed, when it was administered alone at a dose of 1 mg, animals were rendered behaviorally unresponsive to a P treatment 25 hr later. It is unclear whether RU 38486 is an agonist for P sequential inhibition of estrous behavior or if the apparent agonist action of RU 38486 actually results from a long-term antagonist effect. Estrogen-induced PRs remain elevated (35–55% above basal) in the hypothalamus (HYP) and preoptic area (POA) at 24 and 48 hr following the last estrogen injection. Thus P facilitation of estrous behavior is correlated with increased levels of cytosol PRs. RU 38486 reduced cytosol PRs in both brain regions to basal levels within 2 hr, and the levels remained suppressed 25 hr following the treatment. Hence there is a strong correlation between behavioral inhibition and suppressed cytosol PRs at both short (5 hr) and long (25 hr) intervals after RU 38486 administration. A P treatment which produced sequential inhibition of estrous responsiveness 24 hr later did not reduce the estrogen-induced level of cytosol PRs in either brain region. These results suggest that mechanisms in addition to induction of PRs may be necessary to ensure successful mating.

Temporal aspects of ventromedial hypothalamic progesterone action in the facilitation of estrous behavior in the female rat.

Progesterone (P) action following estrogen priming is required normally for the facilitation of estrous behavior in female rats. Although mechanisms by which P exerts its influence on estrous responsiveness have not been elucidated, the primary site of action of P has been shown to be the ventromedial nucleus of the hypothalamus (VMN). The objective of the present series of experiments was to describe the temporal parameters of P action in the VMN in the facilitation of estrous behavior in estrogen-primed female rats. Subjects were female Long-Evans rats stereotaxically outfitted with 23-ga. guide cannulae directed towards the VMN. Crystalline P was applied directly to the brain tissue via bilateral 28-ga. insert cannulae, which could be inserted and removed easily through the guide cannulae. Animals were ovariectomized and estrogen primed with 5% estradiol Silastic capsules. They received a counterbalanced series of two experimental tests: one involving a manipulation with a P-filled implant, and another with a blank implant. In the first experiment, a significant increase in estrous responsiveness occurred only after 2 hr exposure of the VMN to P, whereas 4 hr were required for a full display of estrous behavior, including solicitation. In Experiment 2, P was lowered into the brain for either 1, 2, or 4 hr, and testing took place 4 hr after the lowering of the implant. It was found that 2 hr of P exposure was sufficient to facilitate full estrous responsiveness at 4 hr. In Experiment 3, it was revealed that the duration of estrous responsiveness was directly related to the time the P implant remained in the brain. In the fourth experiment, the time course of P retention in brain tissue, revealed by determination of 3H-progesterone levels in hypothalamus, agreed with the behavioral findings. Progesterone levels in the region of the VMN remained high while a P implant was in place, but declined rapidly after removal. A dual mechanistic hypothesis for P action in the facilitation of estrous behavior is presented.

Temporal aspects of ventromedial hypothalamic progesterone action in the facilitation of estrous behavior in the female rat.

Temporal aspects of ventromedial hypothalamic progesterone action in the facilitation of estrous behavior in the female rat.