Effects of an estrogen antagonist,MER-25, on mounting behavior and lordosis behavior in the female rat

Four daily injections of 20 mg ethamoxytriphetol, MER-25, to intact female rats with regular 4-day estrous cycles inhibited lordosis behavior, but had no inhibitory effect on mounting behavior. Ten mg/day of MER-25 for 9 days partially antagonized the stimulatory effect of 2 μg/day of estradiol benzoate on lordosis behavior in ovariectomized female rats, but had no inhibitory effect upon mounting behavior. MER-25 (10 mg/day for 9 days) stimulated the display of mounting behavior in ovariectomized female rats. No effects of MER-25 treatment (10 mg for 10 days) comparable to those of testosterone propionate (10, 50, or 250 μg for 10 days) on testicular, seminal vesicle, or ventral prostate weights of intact male rats or on seminal vesicle or ventral prostate weights of castrated male rats were observed. The results show that MER-25 acts differently upon various estrogen sensitive behaviors in the female rat.     

The inhibitory actions of progesterone: effects on male and female sexual behavior of the hamster

A series of three experiments compared the inhibitory effects of progesterone on estrogen- or androgen-induced sexual behavior in male and female hamsters. In the first experiment chronic progesterone treatment was found to have no effect on male copulatory behavior maintained after castration with testosterone propionate or estradiol benzoate. However, testosterone propionate was more effective at maintaining male behavior than estradiol benzoate. In the second experiment progesterone was found to have a slight inhibitory effect on the rate of the restoration of the intromission response after androgen treatment in males which had been castrated for 8 weeks. In the final experiment, chronic progesterone treatment markedly inhibited sexual receptivity in male and female hamsters which had been given 4 weeks of androgen or estrogen treatment and a single pretest injection of progesterone. Thus, progesterone was shown to be a potent inhibitor of androgen- or estrogen-induced estrus in both male and female hamsters. Due to the large difference in effectiveness on these two behavioral systems, we suggest that progesterone affects steroid-induced male copulatory behavior and female receptivity by different mechanisms of action.     

Induction of ear wiggling in the estrous female rat by gonadectomized rats treated with androgens and estrogens

Intact and gonadectomized male and female rats treated with estradiol and/or dihydrotestosterone were introduced into the cage of estrous female rats. For 3 min the number of periods with ear wiggling displayed by the estrous female and the total duration of the periods with ear wiggling were recorded. It was found that estrous females showed about twice as much ear wiggling in the presence of intact males as in the presence of gonadectomized male and female rats. However, gonadectomized male and female rats treated with dihydrotestosterone induced as much ear wiggling as intact males did. In contrast, administration of estradiol to the gonadectomized stimulus rats did not affect the rate of ear wiggling of the estrous females. Estrous females showed the lowest rate of ear wiggling in the presence of intact female rats. It has been suggested that dihydrotestosterone-treated male and female rats have an odor which sexually excites estrous female rats.     

A soy supplement and tamoxifen inhibit sexual behavior in female rats

In addition to displaying proceptive (hopping and darting) and receptive (lordosis) behaviors during a sexual encounter with a male, female rodents will regulate the timing of the encounter by engaging in a series of approaches and withdrawals from the male, a behavior termed paced mating behavior. Proceptive, receptive, and paced mating behaviors are all regulated by, and sensitive to, estrogen and progesterone, suggesting that compounds capable of disrupting these critical hormones may also perturb the display of female sexual behavior. The present experiments examined the impact of the selective estrogen receptor modulator (SERM) tamoxifen and a popular soy phytoestrogen dietary supplement on female sexual behavior in rats. Ovariectomized female rats were given either tamoxifen (TAMOX) by implant or the soy supplement through the diet then injected with estradiol benzoate (EB, 10 microg) or oil followed 48 h later with an injection of progesterone (P, 500 microg). Animals were then tested for sexual behavior 4 h after the P injection. Neither compound had any effect on sexual behavior when administered in conjunction with P alone; however, both significantly diminished receptive behavior, as measured by the lordosis quotient (LQ), in animals primed with both EB and P. Similarly, the hopping and darting rate was also significantly depressed in both the soy- and TAMOX-treated animals, compared to the EB- and P-treated controls, with the soy-treated animals showing significantly less proceptive behavior than the TAMOX-treated animals. Finally, soy but not TAMOX significantly attenuated paced mating behavior in animals compared to the EB- and P-treated controls. These results demonstrate that both the soy supplement and TAMOX act as estrogen antagonists on both proceptive and receptive behavior in female rats.     

Adult partner preference and sexual behavior of male rats affected by perinatal endocrine manipulations

Intact adult male rats, in which aromatization of testosterone to estradiol was prevented pre- and/or neonatally by ATD (1,4,6-androstatriene-3,17-dione), were repeatedly tested for partner preference behavior (choice: estrous female vs active male). In consecutive tests increasing preference scores for the female were found. Neonatal ATD males showed significantly lower preference scores for an estrous female than controls or prenatal ATD males. Prenatal ATD caused preference scores only slightly lower than those of controls. Ejaculation frequencies were markedly reduced or even absent in neonatal ATD males. Prenatal ATD treatment only had no or a moderately lowering effect on ejaculation frequency. Lordosis behavior of adult intact males was more facilitated following neonatal ATD treatment than following prenatal ATD treatment. In a number of tests the serotonergic drug 8-OH-DPAT was injected prior to testing for sexual partner preference and copulatory behavior. DPAT significantly increased preference for an estrous female in all groups of males when interaction was possible, but had no effect when sexual interaction was prevented by wire mesh. DPAT was able to increase the number of ejaculators in nonejaculating groups (i.e., perinatally ATD-treated males). "Premature ejaculations," i.e., ejaculations with the first intromission, were frequently observed with DPAT treatment in all groups of males. In conclusion, the availability of neonatal estrogen (derived from testosterone) organizes, at least partially, the preference for an estrous female normally shown by adult male rats. The lack of neonatal estrogen causes males to be less masculinized, both in partner preference behavior and ejaculatory behavior, and less defeminized in lordosis behavior.(ABSTRACT TRUNCATED AT 250 WORDS)     

Solicitation behavior in the estrous female rat: a review

Data are reviewed concerning the display of solicitation behaviors in the estrous female rat, including precopulatory hopping, darting, and ear wiggling, and the pacing of copulatory contacts through patterns of approach toward and withdrawal from a sexually active male rat. Observations made under semi-natural and laboratory conditions suggest that solicitation behaviors determine the types and amounts of coital stimuli received by the female. Solicitation behaviors as regulators of cervical-vaginal stimulation play a primary role in ensuring the activation of the neuroendocrine reflex are responsible for prolongation of ovarian corpora luteal function. Despite solicitation behaviors' importance for reproductive success, few studies have examined the neural and endocrine mechanisms involved in the display of those aspects of solicitation behavior which influence the patterning of coital stimuli received by the female. The present review suggests that two elements of pacing behavior, the ability to discriminate between varying intensities of coital stimulation and the active patterning of approach/withdrawal which controls receipt of that stimulation, are constituent parts of solicitation behaviors readily amenable to experimental investigation.     

Natural or hormone-induced sexual and social behaviors in the female brown lemming (Lemmus trimucronatus)

The behaviors of intact or ovariectomized, estradiol benzoate-treated or estradiol benzoate followed by progesterone-treated female brown lemmings were compared. Intact, diestrous females engaged in more social interactions with a male than did ovariectomized females (Experiment 1). In the first 5 min of a 1-hr mating exposure (Experiment 2, Test A) intact females in natural estrus engaged in more social and sexual behaviors than did ovariectomized females in estrogen-induced estrus. However, during the last 5 min of the 1-hr exposure (Test B) ovariectomized females receiving estrogen alone continued to show high levels of sexual activity with a male partner, while intact estrous females or females receiving estrogen followed by progesterone showed an apparent drop in sexual receptivity and an increase in aggressivity. Aggressive behaviors, as indexed by threat-leap behaviors on the part of the female may increase in the presence of progesterone. Declines in sexual activity, occurring within 1 hr of progesterone injection, were apparently dependent on the interaction of progesterone and copulatory events which may affect both the male and female.     

Sexual partner preference requires a functional aromatase (cyp19) gene in male mice

Sexual motivation, sexual partner preference, and sexual performance represent three different aspects of sexual behavior that are critical in determining the reproductive success of a species. Although the display of sexual behavior is under strict hormonal control in both sexes, the relative roles of androgen and estrogen receptors in activating the various components of male sexual behavior are still largely unknown. A recently developed mouse model that is deficient in estradiol due to targeted disruption of exons 1 and 2 of the Cyp19 gene (aromatase knockout (ArKO) mice) was used here to analyze the role of estradiol in the control of all three aspects of male sexual behavior. When tested in a Y-maze providing volatile olfactory cues, male ArKO mice did not show a preference for the odors from an estrous female over those from an intact male, whereas wild-type (WT) and heterozygous (HET) males clearly preferred to sniff estrous odors. When provided with visual and olfactory cues, male ArKO mice also failed to show a preference for an estrous female when given a choice between an estrous female and an empty arm. However, sexual partner preferences of male ArKO mice were not sex-reversed: they did not prefer to investigate an intact male over an estrous female or empty arm. Thus, male ArKO mice seemed to have general deficits in discriminating between conspecifics by using olfactory and visual cues. Male coital behavior was also severely impaired in male ArKO mice: they displayed significantly fewer mounts, intromissions, and ejaculations than WT and HET males. Latencies to first mount or intromission were also significantly longer in ArKO males compared to WT and HET males, in addition to them showing less interest in investigating olfactory and visual cues in a Y-maze, suggesting that they were sexually less motivated. However, three out of seven male ArKO mice were capable of siring litters provided they were housed with a female for a prolonged period of time. In conclusion, aromatization of testosterone to estradiol appears to be essential for sexual motivation and sexual partner preference. By contrast, estradiol may play only a limited role in the expression of male coital behaviors.     

Testicular involvement in peripubertal gonadotropin levels and accessory sex organ weight of male hamsters

This study evaluates the influence of testicular secretions during development in male hamsters on peripubertal gonadotropin levels. Castration or sham operations were performed on the day of birth (Day 1), Day 5, 10, or 20 of life. Repeated plasma samples on Days 20-60 at 10-day intervals were taken via orbital sinus puncture. Castrated animals received a subcutaneous testosterone capsule on Day 60 and were killed on Day 70. In addition, seminal vesicles and ventral prostate weights were taken in all animals at Day 70. Castrated animals, regardless of day of castration, had higher gonadotropin levels and suppressed sexual accessory organ weights. Animals castrated on the day of birth had lower luteinizing hormone (LH) levels than animals castrated on other days. Castration on Day 10 resulted in lower follicle stimulating hormone (FSH) levels. Males castrated on Day 20 were most sensitive to the negative feedback effect of testosterone on LH secretion, while Day 10 castrates had elevated FSH levels after testosterone exposure. Sexual accessory weights also differed depending upon the day of castration. Results point out the importance of testicular secretions on the developmental processes as well as the differing ages at which various systems may be influenced.     

Dose-response and time-response relationships between progesterone and the display of patterns of receptive and proceptive behavior in the female rat

The relationship between administration of progesterone and the display of patterns of receptive (response to the male) and preceptive (female initiated) sexual behavior was examined in ovariectomized, estrogen-primed female rats in a “restrained male” test situation. It was found that the degree of receptivity and proceptivity displayed was directly proportional to progesterone dose and time from progesterone injection (up to 4.5 hr). Higher progesterone doses and longer period of time from progesterone injection (up to 4.5 hr) were both associated with shorter latencies to return to the male following intromission and ejaculation. Receptivity could be induced with estrogen alone but progesterone was required for the display of proceptivity and higher doses of progesterone were needed to effect increases in proceptivity relative to receptivity. Proceptive behavior also occurred in a narrower time range than did receptive behavior. Receptivity alone is characterized as the lowest degree, and receptivity plus proceptivity as the highest degree, of expression of the total behavior pattern of the estrous female rat. Receptivity and proceptivity together constitute a continuum of estrous responsiveness. Increasing the progesterone dose from 0 to 200 μg, and increasing the latency from progesterone injection from 0 to 4.5 hr, were associated with increasing degree of expression of the total behavioral continuum.     

Potential contribution of prenatal estrogens to the sexual differentiation of mate preferences in mice

The neural mechanisms controlling sexual behavior are sexually differentiated by perinatal actions of gonadal hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estrogens, that exposure to prenatal estrogens completely defeminized their potential to show lordosis behavior in adulthood. Therefore, we determined here whether mate preferences were also affected in female AFP-KO mice. We observed a robust preference for an estrous female over an intact male in female AFP-KO mice, which were ovariectomized in adulthood and subsequently treated with estradiol and progesterone, whereas similarly treated WT females preferred the intact male over the estrous female. Gonadally intact WT males preferred the estrous female over the male, but only when visual cues were blocked by placing stimulus animals behind opaque partitions. Furthermore, when given the choice between an intact male and a castrated male, WT females preferred the intact male, whereas AFP-KO females showed no preference. Finally when given the choice between an estrous female and an ovariectomized female, WT males preferred the estrous female whereas AFP-KO females preferred the ovariectomized female or showed no preference depending on whether they could see the stimulus animals or not. Taken together, when AFP-KO females are tested under estrous conditions, they do not show any male-directed preferences, indicating a reduced sexual motivation to seek out the male in these females. However, they do not completely resemble males in their mate preferences suggesting that the male-typical pattern of mate preferences is not solely organized by prenatal estrogens.     

The postnatal demasculinization of sexual behavior in the Japanese quail (Coturnix coturnix japonica)

Three experiments were performed to analyze the time course of demasculinization in the Japanese quail and to test the activating and organizing effects of estradiol (E2) in adult sexually active birds. In Experiment 1, males and females were castrated at the age of 1 day or 1, 2, 4, and 6 weeks and treated as adults with testosterone (T). The age of castration had no effect on behavior and morphology in males. Plasma gonadotrophins (LH and FSH) were, however, higher in males castrated at or before than in those castrated after 2 weeks of age. This suggests that postnatal testicular secretions have organizing effects on the pituitary activity. Females which were castrated before 1 week of age were less sensitive to the activating effects of T than males, but were not fully demasculinized. The demasculinization of different reproductive characteristics such as male sexual behavior, cloacal gland size, and weight of the syringeal muscles is achieved in females at different times posthatching. In Experiment 2, castration of male and female quail at the ages of 4 days or 4 weeks confirmed that postnatal ovarian secretions contribute to the full behavioral and morphological demasculinization of females. It is easier to elicit mounting in T-treated females when they are tested in their home cage instead of a test arena. This difference was not observed in males. During Experiment 3, it was impossible to demasculinize sexually active adult males or females by treatment with Silastic implants of E2. E2 did not maintain sexual behavior in ovariectomized females showing male sexual behavior when treated with T but maintained the behavior in males.     

Psychobiology of sexual behavior in a whiptail lizard, Cnemidophorus inornatus

This study investigated the effects of social environment on gonadal recrudescence and sexual behavior in male and female Little Striped Whiptail lizards (Cnemidophorus inornatus). The presence of sexually active males facilitates ovarian recrudescence in conspecific females. Similarly, the presence of reproductively active females facilitates testicular recrudescence in conspecific males. Males housed with females, however, had lower average circulating concentrations of testosterone and dihydrotestosterone, and higher average concentrations of corticosterone compared to intact males housed in isolation. In other studies, the presence of reproductively active females partially restored courtship behavior in castrated males compared to castrated males housed in isolation. Despite the stimulatory effects of females on castrates, exogenous androgens are required for complete restoration of all components of sexual behavior in male C. inornatus. Females are receptive to male courtship and copulatory behavior only during the vitellogenic stages; females in previtellogenic or postovulatory ovarian stages aggressively reject male courtship advances. These findings demonstrate reciprocal effects of sexual behaviors of males and females upon each other's reproductive behavior and physiology.     

Effect of sexual steroids and androgen sterilization on avoidance and exploratory behaviour in the rat

The effect on avoidance and exploratory behavior of large doses of sexual steroids or of changes in ovarian steroid secretion induced by gonadotropin treatment or androgen sterilization was studied in female R-Amsterdam rats. Estrogen, progesterone, testosterone, androgen sterilization, and human chorionic gonadotropin (HCG) effects were tested and evaluated. Estrogen in castrated female rats delayed extinction of the conditioned avoidance response from Day 8 of extinction and increased intertrial activity during extinction. Estrogen treatment applied from extinction was ineffective. Progesterone treatment of castrated female rats applied from the first days of conditioning delayed extinction from Day 12. If the treatment was begun at extinction, this was delayed after Day 8. Intertrial activity was also higher between Day 8 and Day 15 of extinction. Testosterone treatment of castrated male rats increased intertrial activity during acquisition. In the animals treated from extinction, a delay was observed from Day 9, and intertrial activity was increased simultaneously. In androgen-sterilized female rats, extinction was facilitated. HCG treatment of intact female rats delayed the extinction. The steroids used failed to affect the exploratory activity of castrated rats, indicating that, under the conditions tested, general activity and exploratory activity are not motivated by the same mechanism.     

Exogenous androgen during development alters adult partner preference and mating behavior in gonadally intact male rats

In the rat, neonatal administration of testosterone propionate to a castrated male causes masculinization of behavior. However, if an intact male is treated neonatally with testosterone (hyper-androgen condition), male sexual behavior in adulthood is disrupted. There is a possibility that the hyper-androgen treatment is suppressing male sexual behavior by altering the male's partner preference and thereby reducing his motivation to approach the female. If so, this would suggest that exposure to supra-physiological levels of androgen during development may result in the development of male-oriented partner preference in the male. To test this idea, male rats were treated either postnatally or prenatally with testosterone, and partner preference and sexual behavior were examined in adulthood. The principal finding of this study was that increased levels of testosterone during early postnatal life, but not prenatal, decreased male sexual behavior and increased the amount of time a male spent with a stimulus male, without affecting the amount of time spent with a stimulus female during partner preference tests. Thus, the reduction in male sexual behavior produced by early exposure to high levels of testosterone is not likely due to a reduction in the male's motivation to approach a receptive female.     

Effect of newborn rat testes on the male sexual behavior of the testosterone-treated adult

Neonatal male rats were castrated either at 0, 6 or 24 hrs. after birth. As adults, testosterone was delivered by subcutaneous implantation of a Silastic capsule containing this hormone. The probability to display mounting behavior in presence of an estrous female was lower when the animals were castrated at 0 hr. than at 6 or 24 hrs. or when they received a subcutaneous injection of 1 microgram of testosterone propionate, at the time of castration at 0 hr. These results suggest that in the rat, during the 6 hrs. following birth, neonatal testes influence the sensitivity of the adult central nervous system to testosterone.     

Control of proceptive and receptive behavior by ovarian hormones in the Syrian hamster (Mesocricetus auratus)

Two studies examined the roles of estrogen with progesterone and of estrogen alone on the proceptive and receptive behavior of female hamsters. Proceptivity was measured in terms of proximity (approaching, leaving, and following by the female) and in time spent sniffing the male partner. During the 4-day natural estrous cycle, these measures change systematically although lordosis is seen only on Day 1 (estrus). With a constant dose of progesterone, both proceptive and receptive behavior were found to be estrogen dose dependent in ovariectomized females. At estrogen levels too low to induce lordosis, changes in proceptive behavior were seen; at the two highest levels of estrogen, lordosis was maximal but proceptive behavior continued to increase. With estrogen alone, levels of proceptive behavior were attained characteristic both of estrus and of the higher estrogen and progesterone dosage but were not accompanied by spontaneous lordosis. Factors indicating that proceptivity and receptivity may be under separate hormonal and neural control are discussed.     

Maturation of social reward in adult male Syrian hamsters does not depend on organizational effects of pubertal testosterone

The rewarding value of female sexual stimuli develops across puberty, as sexually-naïve adult, but not prepubertal, male hamsters show a conditioned place preference (CPP) for both vaginal secretions and a receptive female. Similarly, only adults show an endogenous testosterone surge when they encounter vaginal secretions. Testosterone by itself can condition a place preference in male rodents. Therefore, Experiment 1 assessed whether the endogenous testosterone surge elicited by vaginal secretions is necessary to show a CPP. Both gonad-intact and gonadectomized, testosterone-treated adult males showed a CPP for vaginal secretions, indicating that the rewarding value of this social cue is independent of an endogenous testosterone surge. However, organizational effects of pubertal testosterone could be necessary for adolescent development of social reward, as pubertal testosterone organizes adult-typical expression of sexual behavior. To investigate this possibility, in Experiment 2, sexually-naïve prepubertal and adult male hamsters were gonadectomized and received testosterone-filled capsules four weeks later. Testing began after two weeks of testosterone replacement. Adult males showed a CPP for both vaginal secretions and a receptive female, whether or not they experienced pubertal testosterone. Thus, the acquisition of positive valence of sexual stimuli is not organized by pubertal testosterone. Taken together, the ability of female sexual stimuli to serve as an unconditioned reward to adult male hamsters is independent of the chemosensory-induced endogenous testosterone surge and also organizational effects of pubertal testosterone. Instead, sexual reward may be dependent either on activational effects of testosterone or gonadal hormone-independent mechanisms.     

Estrogen-activated sexual behavior in male rats

Daily injections of 100 μg estradiol benzoate activated the whole pattern of sexual behavior in castrated sexually experienced male rats. If compared to rats treated daily with 100 μg testosterone propionate, the estrogen-treated males tended to have longer latencies and more mounts and intromissions prior to ejaculation. Fifty micrograms of estradiol benzoate stimulated the display of mounts and intromissions in prepuberally castrated male rats. No peripheral effects of the estrogen treatment were noted. These results suggest that estrogen has central “androgen-like” effects, but no such effects in the periphery. Estrogen treatment (5, 50, and 200 μg/kg for 3 weeks) of intact sexually experienced male rats resulted in testicular atrophy and loss of body weight, but had no significant effects on the sexual behavior.