A possible involvement of adrenaline in the facilitation of lordosis behavior in the ovariectomized rat

In order to examine a possible role of adrenaline (AD) or noradrenaline (NA) in the control of lordosis behavior, lordosis quotient (LQ) was observed daily for 8 consecutive days in the ovariectomized rat given daily 1 or 2 microgram/0.1 ml oil of estradiol benzoate (EB) alone or together with 100 microgram/0.1 ml saline of AD or NA. AD but not NA treated together with EB caused a greater change in the daily LQ than the same dose of EB alone and the change in the daily LQ by daily treatment with both 1 microgram EB and 100 microgram AD was equivalent to that by daily treatment with 2 microgram EB alone. A half mg progesterone (P) could induce the lordosis behavior in the ovariectomized rat treated 48 hr prior with both 1 microgram EB and 50 or 100 microgram AD, but not in the one treated with 1 microgram EB alone. While 50, 100 or 200 microgram NA or 10 microgram AD had no effect, 50 or 100 microgram AD pretreated together with 2 microgram EB produced a markedly higher LQ after P than 2 microgram EB alone in the ovariectomized rat. This effect of AD on the induction of lordosis behavior was produced only when AD was pretreated simultaneously with EB and AD priming 24 or 43 hr after EB failed to elicit the effect. Therefore, it is suggested that a change of the brain target site in the estrogen sensitivity produced by AD plays a part in the control of lordosis behavior.     

Effects of the antiestrogens,MER-25 and CI 628, on rat and hamster lordosis

Antiestrogens were used to test the hypothesis that estrogen exerts a “maintenance,” as well as a “priming,” effect on rat and hamster sexual receptivity as it apparently does for guinea pigs. MER-25 (75 or 150 mg/kg) significantly reduced rat LQ when given ?2 hr or 8 hr after EB injection. MER-25 given at 34 hr (2 hr prior to P) failed to diminish rat LQ. With hamsters, MER-25 in large doses (750 mg/kg) given either at ?2 hr or 34 hr reduced lordosis duration to 40% of controls, but this effect was confounded by severe illness among the MER-25 injected animals. Lower doses failed to block behavior, but still produced some toxicity. CI 628 (50 mg/kg) greatly reduced hamster lordosis duration and increased lordosis latency when given 0 hr, but not 34 hr, after EB. The results are consistent with similar previous work on rats and do not support the concept of estrogen “maintenance” in either rats or hamsters.     

Facilitation of receptive behavior in estrogen-primed female rats by the anti-progestin, RU 486

The progestin receptor antagonist RU 38486 (henceforth referred to as RU 486) was tested for facilitative effects on female receptive behavior in ovariectomized Long-Evans rats primed with 2 micrograms estradiol benzoate (EB). RU 486 (0, 0.5, 1.6, or 5.0 mg) was administered 48 hr after estrogen priming. The lordosis quotient (LQ) and lordosis score (LS) were assessed 4 hr after RU 486 administration in a standardized test consisting of a 10-mount test by a stimulus male. A significant dose effect was found by both LQ and LS, with those subjects receiving 5 mg of RU 486 being significantly more receptive than vehicle control animals. Thus RU 486 acted as a weak progestin agonist under testing conditions typical for assessment of progestin facilitation of female sexual behavior in rats. Low levels of proceptive behavior (hops and darts) were seen in a minority of the tests, and did not vary systematically as a function of the dose of RU 486 administered. We also examined the effects of RU 486 given before progesterone (P) on receptivity in a blocking paradigm and confirmed previous reports that the antagonist significantly attenuates facilitation of sexual behavior when given in combination with P. A progestin receptor assay of the cytosols of the hypothalamus-preoptic area in estrogen-primed female rats treated with 5 mg RU 486 revealed a significantly greater depletion of available cytosolic P receptors than when rats were treated with a similarly facilitating dose of P (100 micrograms). The results suggest a possible dual mode of action for RU 486--a weak, receptor-mediated agonistic effect on sexual behavior when given alone to estrogen-primed rats, and a competitive blocking effect on receptivity when administered with P.     

Cytoplasmic progesterone receptors in the hypothalamus-preoptic area of the mouse: effect of estrogen priming

A synthetic progestin, R5020, was used to identify cytoplasmic progestin receptors in the hypothalamuspreoptic area (HPOA) of ovariectomized mice. These high-affinity receptors exhibited an apparent dissociation constant of approx. 1 nM. The receptors were specific for progestins. [3H]R5020 binding was inhibited by more than 50% with a 50-fold excess of either radioinert R5020 or progesterone. 5 alpha-Dihydroprogesterone inhibited binding to a lesser extent. 3 alpha-Hydroxy-5 alpha-pregnane-20-one and cortisol did not compete for [3H]R5020 binding. Administration of estradiol benzoate (10 micrograms), 48 h prior to death, resulted in a 54% increase in the HPOA progestin receptor concentration when compared to oil-injected controls. These data demonstrate that there are specific and saturable cytoplasmic progestin receptors in the mouse HPOA and that the concentration of these receptors is increased after estrogen treatment.     

Attenuating the defeminization of the neonatal rat brain: Mechanisms of action of cyproterone acetate, 1,4,6-androstatriene-3,17,-dione and a synthetic progestin, R5020

Although defeminization of the rat brain appears to depend significantly on the conversion of testosterone (T) to estradiol (E₂), the antiandrogenic steroid cyproterone acetate (CA) is able to attenuate defeminization. In order to study the mechanism of action of CA on brain sexual differentiation, newborn male rats were given subcutaneous injections of this steroid on postnatal Days 2–6. When castrated on Day 70 and given estrogen and progesterone, these CA-treated males displayed elevated lordosis quotients (LQ) compared to controls. CA-treated neonatal males were also examined at the end of the drug treatment to ascertain the mechanism of drug action: (1) Serum T levels were normal; (2) Brain cell nuclear estrogen receptor occupation, estimated by an exchange assay, was reduced by ≈ 30% in the brains of the CA-treated males, although the ability of exogenous E₂ to occupy these brain estrogen receptors was not reduced. Other work has demonstrated a weak competitive effect of cyproterone on aromatization, and thus cyproterone acetate may have interfered with the conversion of T to E₂ CA also has progestogenic activity, and 5-mm capsules of a potent synthetic progestin, R5020, given to newborn male rats on Days 2–6, are shown to elevate the LQ after postnatal Day 70 to the same extent as CA. However, R5020 did not reduce estrogen receptor occupation in the neonatal male rat brain and was without effect on serum T levels in the neonatal male. Because of the implied role of T-derived estrogens in defeminization, an experiment was conducted showing that the defeminizing action of estradiol benzoate given to 3-day-old female rat pups is attenuated by the antiestrogen, CI628, and not by the potent inhibitor of aromatization, 1,4,6-androstatriene-3,17-dione (ATD). This result complements previous experiments showing that both ATD and CI628 attenuate the defeminization produced by T. Taken together, the results lend further support to a pivotal role for aromatization and for estrogen-receptor interactions in the defeminizing effects of T. The actions of progestins such as CA and R5020 in attenuating defeminization are discussed in relation to the recent demonstration of progestin receptors in the neonatal rat brain. It is concluded that CA may act by a combination of actions, both by inhibiting aromatization and by acting as a progestin.     

Effects of septal lesions on behavioral sensitivity of female rats to gonadal hormones

Spayed female rats were given bilateral septal lesions or a sham operation and 3 wk later tested for hormone-induced female sexual behavior. When primed with 0.5, 1.0, or 2.0 μg of estradiol benzoate (EB) per day for 3 days and tested for lordosis behavior on the fourth day, animals with septal lesions showed a positive dose-related increase in mean lordosis quotient (LQ), whereas control animals showed a low mean LQ for all doses of EB. After priming with a low dose of EB (0.5 μg/day for 3 days), progesterone administration prior to behavior testing on day 4 produced a comparable facilitation in LQ for both septal-lesioned and sham-operated animals. When treated for 3 days with either 50 or 150 μg of testosterone propionate (TP) and given progesterone prior to behavior testing on day 4, female rats with septal lesions showed a higher mean LQ than sham-operated rats. Thus, septal lesions increase the behavioral sensitivity of female rats to both EB and TP as measured by female sexual behavior, but do not appear to alter the responsiveness of animals to progesterone.     

Inhibition of estrogen facilitation of sexual behavior by the intracerebral infusion of actinomycin-D

It has been shown previously that intracerebral actinomycin-D (Act-D) pellets inhibit estrogen facilitated female sexual behavior, but it was not possible to test the reversibility of this effect. In the present study an attempt was made to distinguish between the possible temporary interruption by Act-D of the biochemical action of estrogen which facilitates sexual receptivity and permanent toxic effects of the drug. Act-D in saline was infused into the third ventricle or the preoptic area (POA) to determine whether a reversible suppression of sexual behavior as measured by the lordosis quotient (LQ) could be produced. Ovariectomized rats were implanted with midline guide tubes entering the third ventricle (eight rats) or with bilateral tubes extending to the corpus callosum above the POA (67 rats). Each animal served as its own control since pretest and Act-D and recovery tests were performed 10–14 days apart in most subjects. For each behavioral test implanted subjects were primed with 3μg estradiol benzoate (EB) and 0.5 mg progesterone (P) 48 hr later. Behavioral tests, each involving 50 mounts, were performed 4–6 hr after P. Following the pretest the animals were retested under experimental conditions. Inner cannulae were inserted into the POA through the guide tubes and 0.11 μg Act-D infused 24 or 12 hr before, simultaneously with, or 6, 12, 18, or 26 hr after EB. A recovery test was performed 10–14 days later with no intracerebral infusion. The control procedure (infusion of of saline either simultaneously with or 12 hr after EB) did not alter the LQ. Act-D infusion produced a reversible suppression of lordosis which was dependent upon the time of administration of Act-D. Intraventricular infusion of Act-D 6 hr after EB reversibly inhibited lordosis behavior and no lesions were produced. Act-D infused into the POA simultaneously with EB or 6 hr later reversibly suppressed the LQ. In the 6 hr group, for example, the LQ fell from 78.3 to 35.7, but 10–14 days later reached 74.3. Although brain lesions of varying extent were produced by Act-D, the marked but reversible suppression of lordosis behavior is consistent with the view that Act-D inhibits estrogen facilitation of lordosis behavior by means of a biochemical rather than cytotoxic action.     

Inhibition of estrous behavior in rats by intrahypothalamic application of agents that disrupt nuclear binding of estrogen-receptor complexes

This study tested the hypothesis that estrogen facilitation of reproductive behavior in female rats requires the binding of estrogen-receptor complexes to the genomic components of hypothalamic cell nuclei. Female rats were implanted stereotaxically with bilateral guide cannulae aimed at the ventromedial nucleus of the hypothalamus (VMH). Animals were ovariectomized following recovery from the implant surgery and randomly assigned to receive one of four drug treatments: actinomycin-D, ethidium bromide, netropsin, or 4', 6-diamidino-2-phenylindole. Each female received at least two tests for estrous behavior 48 hr after estrogen priming. On one test, drug-filled cannulae were lowered into the VMH 1 hr prior to a subcutaneous injection of 2-3 micrograms of estradiol benzoate (EB); on the other test blank cannulae were inserted 1 hr prior to EB treatment. Intracranial administration of all four compounds, which disrupt estrogen-receptor binding to hypothalamic nuclei, inhibited both the quantity and the quality of lordosis responses to systemic injections of EB. The results support the hypothesis that specific receptor interactions with the genome of hypothalamic cells mediate estrogen facilitation of estrous behavior in female rats.     

Suppression of lordosis in guinea pigs by ethamoxy-triphetol (MER-25) given at long intervals (34-46 hr) after estradiol benzoate treatment

Ovariectomized guinea pigs were given estradiol benzoate (EB) followed 40 hr later by progesterone (P). Behavioral testing commenced 1 hr after P injection and continued at hourly intervals for 8 hr. This treatment activated lordosis in almost 100% of animals. Administration of the antiestrogen MER-25 (75 mg/kg body wt per injection) between 2 hr before and 6 hr after EB treatment did not cause a significant decline in proportion of animals displaying lordosis, but did cause a decrease in length of time the lordosis position was held (maximum lordosis, sec). In contrast, $\text{13}\text{14}$ animals given MER-25 at 2 hr before and 2 hr after P and $\text{8}\text{10}$ animals given MER-25 simultaneously with and 2 hr after P, failed to show lordosis. Administration of supplementary EB at around the time of P injection, partially alleviated these behavior-blocking effects of MER-25. When MER-25 was given 2–6 hr after administration of P there was a significant decrease in duration of heat (hr). These results suggest that in addition to its early “triggering” effects, estrogen has important “maintenance” effects which determine the character of heat in guinea pigs. Continued presence of estrogen in the nervous system may be a requirement for the facilitatory actions of P on sexual behavior in guinea pigs, but such a requirement may not exist in other rodents such as rats.     

Facilitation of female sexual behavior in male rats by septal lesions: an interaction with estrogen.

Although destruction of the septal region markedly facilitates the lordosis behavior of female rats in response to estrogen priming, comparable lesions were found to be ineffective in facilitating the lordotic behavior of estrogen primed male rats. Neither the age at the time of septal destruction nor castration influenced the lordosis behavior of males. However, if prepubertal castrated males were given subcutaneous ovarian grafts or injected daily with 2 μgm estradiol benzoate (EB) during the 30 day period following septal destruction, a prolonged facilitation of the activational effects of EB on lordosis behavior was observed. Male rats subjected to septal destruction alone, chronic exposure to EB alone, exposure to ovarian grafts for 30 days prior to septal destruction, or chronic treatment with EB started 6 mo after septal lesioning, failed to show an increase in behavioral responsiveness to estrogen. Thus, in order for septal lesions to facilitate lordosis behavior of male rats, exposure to EB or ovarian tissue must occur within an apparent critical period following septal destruction. Adult male rats were found to be more responsive to this interaction of septal lesions and EB exposure than pubertal animals. It is suggested that the prolonged facilitation of lordosis behavior which follows septal destruction and estrogen exposure in the male rat may be due to hormonal modifications of the recovery process following brain damage.     

Effects of serotonin agonists on lordosis,myoclonus, and cytoplasmic progestin receptors in guinea pigs

Peripheral treatment with the serotonin releaser fenfluramine or the serotonin agonist quipazine abolished lordosis behavior in ovariectomized estradiol and progesterone-primed female guinea pigs. Quipazine was also effective when administered into a lateral cerebroventricle. The lowest dose of fenfluramine that induced myoclonus (10 mg/kg) was higher than the dose needed to inhibit lordosis (5 mg/kg). Therefore, it appears that myoclonus and lordosis are differentially sensitive to serotonin agonists. The effects of quipazine on lordosis were time dependent. Quipazine had no effect on lordosis when given prior to the onset of sexual receptivity. These data suggest that serotonin agonists might be effective only when progesterone has had sufficient time to induce sexual receptivity. Quipazine did not affect cytoplasmic progestin receptors in brain areas involved in steroid hormone effects on lordosis. This finding, and the finding that quipazine had no effect on lordosis when given prior to the onset of sexual receptivity, suggest increased serotonin transmission does not interfere with estrogen priming or sensitivity of hypothalamic cells to progesterone.     

The display of sexual behaviors by female rats administered ICI 182,780

ICI 182,780 (ICI) is a pure antiestrogen that when administered systemically does not cross the blood-brain barrier, thus its actions are limited to the periphery. Four experiments were conducted to test the effects of ICI on the display of sexual behaviors in ovariectomized rats. Experiment 1 examined the effects of three doses of ICI (250, 500, and 750 μg/rat) on sexual receptivity and paced mating behavior in rats primed with estradiol benzoate (EB) in combination with progesterone (P). Experiments 2 and 3 compared the display of sexual behaviors in rats primed with EB+P or EB alone and administered either 250 μg ICI (Experiment 2) or 500 μg ICI (Experiment 3). Experiment 4 tested the effects of ICI (250 and 500 μg) on the expression of estrogen-induced progestin receptors in the uterus. ICI did not affect the display of sexual receptivity in any experiment. In rats primed with EB+P, paced mating behavior was altered by the 500 and 750 μg, but not the 250 μg, doses of ICI. The lowest (250 μg) dose of ICI did alter paced mating behavior in rats primed with EB alone. The effects of ICI on paced mating behavior were manifested by a substantial lengthening of contact-return latencies following intromissions and ejaculations. The percentage of exits were not affected by ICI. Estrogen stimulation of uterine weight and induction of uterine progestin receptors was suppressed by ICI (250 and 500 μg). ICI effects on paced mating behavior in hormone-primed female rats are likely to reflect antiestrogenic actions in the periphery, including interference with the estrogen induction of progestin receptors.     

The comparative potency of various steroids to complete the priming process for lordosis in guinea pigs

Ovariectomized adult guinea pigs were treated with a regimen of estradiol benzoate (0.2 μg/animal estradiol benzoate at hr 0 and 19) that was shown to be minimally effective for the induction of lordosis. They were then treated with 10, 20, or 80 mg of enclomiphene, 5, 20, 40, or 100 μg of estradiol, or testosterone, cortisol, estrone, estriol, diethylstilbestrol, catechol estradiol, or catechol estrone (all at a dose equivalent to 5 μg of estradiol) at hr 28. At hr 39 all females were given 0.5 mg progesterone, and subsequently tested for lordosis behavior. Of the various agents injected at hr 28 only estradiol (at all doses given), estrone, estriol, and diethylstilbestrol were effective in supporting display of lordosis behavior. The results indicate that the antiestrogen enclomiphene, the catechol estrogens, and at least some C₁₉ and C₂₁ steroids are weaker than E₂ or ineffective in facilitating lordosis behavior when given late in the priming period. Because previous work had shown that enclomiphene has partial estrogenic effects on lordosis behavior when administered early in the priming period (i.e., at hr 0, 19), it is suggested the early and late phases of the priming process induced by E₂ entail qualitatively different neural processes.     

Antagonism of central estrogen action by intracerebral implants of tamoxifen

In order to determine the neural site(s) of estradiol (E2) priming of receptive behavior in female Long-Evans rats, we attempted to inhibit the behavioral effects of peripheral injections of E2 by administering the E2 antagonist tamoxifen (TX) to particular brain regions. Crystalline TX was administered unilaterally or bilaterally via 28-gauge cannulae into the ventromedial hypothalamic nucleus (VMN), the preoptic area (POA), or the interpeduncular region (IP) 1 hr prior to the first of three daily E2 benzoate injections. Subjects were tested for the presence or absence of behavioral estrus 5 hr after a 200-micrograms progesterone injection given 4 days after the initial hormone treatment. Results of this experiment showed that TX inhibits lordosis when directed toward the VMN, but not when directed toward the POA or IP. The quality of the lordosis response and the proportion of subjects showing solicitation behavior were both lower in VMN subjects treated with TX than in POA or IP subjects given the same treatment. Unilateral implants were as effective as bilateral implants in inhibiting the behavior of VMN subjects. A second experiment measured uptake of radiolabeled E2 by nuclei of hypothalamic (HYP) and POA tissue following bilateral TX administration to the VMN or POA. TX was capable of inhibiting uptake of [3H]E2 into nuclei of cells located near the implant site. Most subjects which showed behavioral inhibition also showed a reduction in uptake of [3H]E2 by HYP tissue. These data support the hypothesis that exposure of the VMN to E2 is necessary for the priming of estrous behavior in the female rat.     

Hysterectomy-induced facilitation of lordosis behavior in the rat

The present study investigated the effect of hysterectomy on hormone-induced lordosis behavior. Lordosis quotients (LQ) were measured in hysterectomized-ovariectomized (HO) and ovariectomized-sham hysterectomized (OSH) rats after several treatments including either estradiol benzoate (EB) alone or EB plus progesterone (P) 44 hr later. Testing consisted of placing the females with sexually active males 48 hr after EB. In Experiment 1, HO animals treated with 5 μg/kg EB and 0.5 mg P had significantly higher LQs than OSH animals; groups treated with 10 μg/kg plus P were not different. Experiment 2 showed that a single injection of 50 μg/kg EB resulted in equally high levels of receptivity in both groups. The LQs of HO animals injected with 3 μg/kg for 4 days did not differ from those of OSH animals; however, the administration of 0.5 mg P 24 hr after the fourth EB injection resulted in significantly higher LQs in the HO group (Experiment 3). In Experiment 4, HO rats injected with 5 μg/kg EB and 0.1 mg P 44 hr later displayed higher levels of lordosis behavior than OSH animals. It was concluded that hysterectomy facilitated the lordosis behavior of ovariectomized rats injected with both EB and P and that the mechanism for this potentiation remains to be determined.     

Hormonal Modulation of the Cutaneous Initiation of Lordosis in Infant and Adult Rats

The purpose of these experiments is to compare the regional specificity (Experiment 1) and the hormonal modulation (Experiment 2) of the cutaneous initiation of lordosis in 4- to 6-day-old male and female rats (infants) and in 60- to 90-day-old female rats (adults). In Experiment 1, subjects were primed with 100 μg estradiol benzoate (EB) and 0.5 mg progesterone (P) and were denervated on the Waist (dermatomes L1-L3), Midriff (dermatomes T10-L3), Flanks (dermatomes L4-L6), or Sides (dermatomes T10-L6). In infants, there were no significant differences between males and females. Denervation of the Waist. Midriff, or Sides but not of the Flanks significantly decreased the percentage of subjects displaying lordosis, lordosis quotient (LQ), and mean lordosis duration; no significant differences were obtained among Waist-, Midriff-, or Sides-denervated infants. In contrast, denervation of the Sides but not of the Waist significantly decreased LQ and mean lordosis intensity among adults. In Experiment 2, Waist-denervated infants and their surgical Controls were treated either with 100 μg EB and 0.5 mg P or with the oil vehicle; Waist-denervated adults and their surgical Controls received either 100 or 10 μg EB (no P). Regardless of hormone treatment, denervation of the Waist significantly decreased LQ and lordosis duration in infants and decreased LQ and lordosis intensity in adults. In infants, the only effect of priming with EB and P was to increase the percentage of pups showing lordosis and lordosis duration among the surgical Controls. In contrast, priming with 100 μg EB significantly increased the percentage of rats displaying lordosis, LQ, and lordosis intensity among Waist-denervated adults. These data suggest that cutaneous input from the Waist is important for eliciting lordosis in both infant and adult rats, and that the importance of this input is modulated by hormone priming in adult but not infant rats.     

Mu-, delta-, and kappa-opioid receptor agonists selectively modulate sexual behaviors in the female rat: differential dependence on progesterone.

Previous studies suggested that opioid receptor agonists infused into the lateral ventricles can inhibit (through mu receptors) or facilitate (through delta receptors) the lordosis behavior of ovariectomized (OVX) rats treated with estrogen and a low dose of progesterone. The present study investigated the behavioral and hormonal specificity of those effects using more selective opioid receptor agonists. Sexually experienced OVX rats were implanted stereotaxically with guide cannulae aimed at the right lateral ventricle. One group of rats was treated with estradiol benzoate (EB, 10 micrograms) 48 hr and progesterone (P, 250 micrograms) 4 hr before testing, whereas the other group was treated with EB alone. Rats were infused with different doses of the selective mu-receptor agonist DAMGO, the selective delta-receptor agonist DPDPE, or the selective kappa-receptor agonist U50-488. The females were placed with a sexually vigorous male in a bilevel chamber (Mendelson and Gorzalka, 1987) for three tests of sexual behavior, beginning 15, 30, and 60 min after each infusion. DAMGO reduced lordosis quotients and magnitudes significantly in rats treated with EB and P, but not in rats treated with EB alone. In contrast, DPDPE and U50-488H increased lordosis quotients and magnitudes significantly in both steroid-treatment groups. Surprisingly, measures of proceptivity, rejection responses, and level changes were not affected significantly by mu or kappa agonists, although proceptivity and rejection responses were affected by DPDPE treatment. These results suggest that the effects of lateral ventricular infusions of opioid receptor agonists on the sexual behavior of female rats are relatively specific to lordosis behavior. Moreover, the facilitation of lordosis behavior by delta- or kappa-receptor agonists is independent of progesterone treatment, whereas the inhibitory effect of mu-receptor agonists on lordosis behavior may require the presence of progesterone.     

Musculinization and defeminization induced in female hamsters by neonatal treatment with estradiol, RU-2858, and nafoxidine

Newborn female hamsters were treated with 0.1 or 1.0 ng of estradiol benzoate (EB), with 1.0 ng–2.0 μg of the synthetic estrogen RU-2858, or with 0.1 or 0.5 μg of the antiestrogen nafoxidine. When adult the animals were treated with EB and progesterone and tested for the display of lordosis and with testosterone propionate and tested for the display of mounting behavior. The EB doses used failed to alter sexual differentiation. RU-2858 masculinized and defeminized in a dose-dependent manner being most effective when given neonatally as two divided doses. Nafoxidine inhibited lordosis without enhancing mounting behavior. The findings support the hypothesis that estrogens may be involved in the normal sexual differentiation process.     

Estrogen and progesterone dose-dependently reduce disruptive effects of restraint on lordosis behavior

Ovariectomized rats were hormonally primed with various doses of estradiol benzoate (EB; 0.5-10 microg) in combination with various doses of progesterone (2.5-500 microg) to induce sexual receptivity. Females were then subjected to 5 min restraint and the effect on lordosis behavior was monitored for the next 30 min. Such mild stress has been previously shown to transiently reduce lordosis behavior of ovariectomized females hormonally primed only with 10 microg EB. In the current study, doses of progesterone of 25 microg or more in combination with 10 microg EB reduced the effects of restraint. Also priming doses of EB from 4.0 to 10 microg in combination with 250 microg progesterone prevented the lordosis-inhibiting effects of restraint. These findings reinforce prior observations of the dose-dependency of both estrogen and progesterone in the facilitation of lordosis behavior and introduce the female's lordosis response to mild restraint as a potentially useful index of the female's response to stress.     

Induction of progestin receptors in the mediobasal hypothalamus of gonadally intact male rats primed with estrogen in relation to display of lordosis behavior

The purpose of this study was to determine whether the effects of estrogen on lordosis behavior in the male rat were related to the number of progesterone (P) receptors in the mediobasal hypothalamus (MBH) and/or dependent on blood P concentration. Two groups of gonadally intact male rats were given five successive doses of 1.0 or 2.5 micrograms estradiol benzoate (EB) and tested for lordosis behavior with a male stimulus at the end of the treatment. One month later they were again injected with EB and sacrificed under the same temporal schedule, but they were not tested for lordosis so as to prevent any emotionally stressful effects of intermale cohabitation. The males given 2.5 micrograms EB more frequently displayed lordosis responses to male mounts than those receiving 1 microgram EB, with a parallel increase in the number of MBH P receptors. The total number of MBH P receptors also appeared to be higher in the animals that displayed lordosis responses (lordosis group) than in those which did not (no lordosis group). In contrast, the display of lordosis behavior was negatively correlated with blood P concentration. Comparing MBH P receptors and blood P values in the EB treated and in nonhormonally treated gonadally intact animals which had been selected for either ability or inability to spontaneously display lordosis behavior, we observed that (1) EB was capable of increasing the number of MBH P receptors in the male rat; and (2) in the absence of EB treatment blood P values were higher in the animals showing lordosis than in those which did not. These data are discussed with respect to observations made in castrated male rats and in ovariectomized females.