Role of estrogens in androgen-induced spontaneous activity in male rats.

Three experiments tested the hypothesis that testosterone may be aromatized to an estrogen to stimulate running-wheel activity in rats. Aromatizable (testosterone propionate: TP) and nonaromatizable (dihydrotestosterone propionate; DHTP) androgens were compared with estradiol benzoate (EB) for the ability to induce running in castrated male rats. The DHTP had no effect on running. The TP increased running, but EB was more than 100 times as effective. A relatively small dose of a specific estrogen antagonist, MER-25, was shown to attenuate the effects of both EB and TP on male running. The MER-25 did not affect the running of castrated, oil-treated male rats and did not inhibit the running induced by food deprivation.     

Steroidal modulation of scent investigation and marking behaviors in male and female ferrets (Mustela putorius furo)

Gonadectomized male and female ferrets (Mustela putorius furo) given either testosterone propionate (TP) or oil vehicle preferred to investigate the side of a test cage previously soiled by a breeding male or female as opposed to a clean side. Male and female ferrets receiving TP showed more urogenital wiping than oil-treated animals in either side of the test cage. In a 2nd experiment, ferrets treated sequentially with TP, oil, and estradiol benzoate (EB) were given simultaneous access to sides of a test cage previously soiled by either a breeding female or male. Either EB or TP treatment of females and TP treatment of males facilitated the investigation of odors of opposite-sex ferrets. Females given TP and males given either TP or EB showed increased urogenital wiping in both sides of the test cage. Sex steroids modulate scent investigation and marking in adult ferrets in a sexually differentiated fashion.     

Interaction between penile reflexes and copulation in male rats

Intact, unanesthetized male rats were place in a supine position, with the penile sheath continuously retracted. Three forms of penile reflex were displayed: erections, cups, and flips. The reciprocal relation between copulation and the penile reflexes occurring in supine tests was explored in four experiments. In Experiment 1, sexual exhaustion depressed all penile reflexes, but the reflexes returned to baseline levels within 8 hr, long before copulatory potential. In Experiment 2, reflexes were depressed to exhaustion levels after fewer ejaculations than were required for sexual exhaustion, an indication that reflexes are more readily evoked during copulation than in supine tests. Experiment 3 determined that a rat's penile-reflex potential may be enhanced by placing the rat in a copulation-test cage, by allowing the male a few antecedent intromissions, or by allowing an antecedent ejaculation. The display of penile reflexes within 1 min after ejaculation suggests that the period of reduced sexual arousability following ejaculation is not due to reduced excitability in the spinal mechanisms controlling penile reflexes. In Experiment 4, 1 hr of penile-reflex elicitation had no effect on subsequent copulatory behavior. Thus, sexual stimulation may increase or decrease penile-reflex potential, but a reciprocal influence was not detectable.     

Effect of novel and familiar mating partners on the duration of sexual receptivity in the female hamster

The lordosis duration of the female golden hamster (Mesocricetus auratus) in response to novel and familiar mating partners was examined. In Experiment 1, females mated to the point of sexual satiation with one male hamster, and following its removal, showed renewed receptivity in response to the introduction of a second male. Upon sexual satiation with the second male, females either received a novel third male or were reexposed to the original male. Total lordosis duration in the third bout in the group receiving a novel male was significantly greater than in the group reexposed to the original male. In Experiment 2, the insertion of a 1-h delay between the second and the third mating partner had no effect on the female's responsiveness, regardless of whether the third male was the original male or a novel male. In Experiment 3, removal of the ovaries followed by hormone replacement treatment (40 micrograms estradiol benzoate, 72 h prior to testing, and 500 micrograms progesterone, 4 h prior to testing) failed to alter the females' ability to discriminate between novel and familiar mating partners. These results demonstrate that females make clear discriminations among individual mating partners, that this can affect sexual receptivity and will continue to do so following a delay of at least 1 h, and that the effect is not mediated by the release of ovarian steroids.     

Evaluation of prenatal androgen and ovarian secretions on receptivity in female and male rats

Offspring of rats infected daily from Day 16 through Day 20 of gestation with either 2 mg of testosterone propionate (TP) in .1 ml of sesame oil or oil alone were tested for sexual receptivity following injections of 3.3 microgram of estradiol benzoate (EB) and .5 mg of progesterone (P) beginning at 40, 80, or 120 days of age. At each age, neonatally gonadectomized males and females from TP-injected litters exhibited less receptivity than corresponding oil-injected controls. Prenatally androgenized females were similar to neonatally castrated oil-injected males at all ages. Ovarian implants from birth to 35 days of age significantly increased receptivity in neonatally castrated males and androgenized females. Increasing the age at which testing was initiated systematically reduced receptivity in all groups.     

Sexual experience and preference for males or females in the female rat

The influence of sexual experience on preference behavior was investigated in adult female rats. In the first experiment, preference behavior for sexually active males versus estrous females was investigated in female rats who were experienced with mounting behavior. Preference of these mount experienced females was compared to preference of females who were naive in this respect. Mount experience with estrous females induced a female-directed preference in ovariectomized female rats, irrespective of whether the females were treated with OIL or with testosterone-propionate (500 micrograms TP, injected once 48 h prior to testing). Sexually naive, OIL-treated females did not show a preference for males or females, but TP induced a preference for a male. Individual differences in mount frequency were not correlated with preference behavior. In the second experiment, the influence of experience with feminine sexual responses on preference behavior was investigated. OIL-treated and TP-treated females oriented equally toward males and females when they had been given the opportunity to copulate with males prior to the preference tests. The results strongly suggest that prior sexual experience is an important determinant of preference behavior. The female's behavior during sexual interactions was, however, not predictive of later preference.     

Hormonal basis of sexual differentiation in the Japanese quail.

On the 10th day of incubation, Japanese quail eggs either were injected with testosterone propionate (TP), estradiol benzoate (EB), or oil, or were not injected. When sexually mature, all birds were examined for a variety of sexually dimorphic behavioral and physical characteristics, both masculine and feminine. They were then exposed to a short photoperiod (causing gonadal regression), treated with either TP or EB, and examined again. Either androgen or estrogen administered before hatching demasculinized males, but did not masculinize females or defeminize either sex. In contrast, early sex hormones masculinize and/or or defeminize mammals. This difference is discussed in relation to other differences in avian and mammalian sexuality.     

Fading to increase heterosexual responsiveness in homosexuals

Heterosexual responsiveness, measured by penile responses and reports of behavior, was strengthened in three homosexuals through a fading procedure. Using two slide projectors, colored slides of nude females were superimposed on colored slides of nude males. As the sexual response was emitted, the nude male was faded out and the nude female faded in. Heterosexual arousal decreased when the fading procedure was reversed or stopped and increased once again when fading was resumed. Homosexual arousal remained high during this experiment but had decreased in two subjects at follow-up. The results suggest that fading was responsible for altering stimulus control of sexual arousal and that aversive techniques may not be necessary in the treatment of sexual deviation.     

Enhanced feminine sexual behavior and infertility in female rats prenatally treated with an antiestrogen

An attempt to elucidate the possible role of prenatal estrogen on the development of feminine sexual behavior and reproductive function was made by treating females with the antiestrogen CI628 prenatally on days 13-19. Control females were prenatally treated with saline or remained untreated. The animals were delivered by caesarian section on day 22 of pregnancy and placed with foster mothers whose newborn pups had been previously removed. Intact peripubertal females in each treatment group were observed for several reproductive measures, including the capacity to become pregnant. Other females were ovariectomized in adulthood and treated with estradiol benzoate (EB) (1, 1.5, 2 or 4 micro g/rat) and 0.5 mg progesterone and tested for receptivity, proceptivity and sexual partner preference. Two weeks after the completion of these tests, the females were injected daily for 7 days with 0.25 mg testosterone and tested for sexual partner preference and mounting behavior. The results obtained showed accelerated vaginal opening, and infertility in the antiestrogen-treated intact females and enhanced receptivity and proceptivity in response to 1 micro g EB in the antiestrogen ovariectomized females. Sexual partner preference and mounting behavior did not differ between groups. These results suggest an involvement of prenatal estrogen on the development of female reproductive function, but not on behavioral differentiation.     

The expression of the genes of aggressiveness in mice: The effect of androgen on aggression and sexual behavior in females

Female mice of strains selectively bred for aggressiveness or nonaggressiveness were injected with testosterone propionate (TF′) at the age of 2 days and as adults, or they were injected as adults only. Aggressive and sexual behavior was then tested with female, receptive female, and male partners before, during, and after the latter TP treatment. The females that had received both TP treatments displayed as much or as little aggression as males of the same strain, leading to the conclusion that aggressiveness genes are not linked with the male sex chromosome, even though they depend on it for their expression. The sexual behavior of the females of both strains that had received both TP treatments was altered to the male type. In the females of the aggressive strain even adult treatment alone was sufficient for this change. Aggressiveness and male sexual behavior would seem to be determined separately, although aggressiveness facilitates the display of male sexual behavior.     

Peripheral and central sex steroids have differential effects on the HPA axis of male and female rats

Sex differences in hypothalamic-pituitary-adrenal (HPA) function were examined in gonadectomized male and female rats given equivalent sex hormone replacement regimens either using subcutaneous silastic implants (Experiment 1) or cannula implants in the medial preoptic area (MPOA) (Experiment 2) containing either dihydrotestosterone (DHT), testosterone propionate (TP), estradiol benzoate (EB), or left empty (control). Plasma was obtained before and after 20 min of restraint stress to determine plasma ACTH, corticosterone, and CBG levels as measures of HPA function. Consistent with the literature, androgens decreased, and estrogen increased these measures of HPA function, although peripheral implants were more effective than MPOA implants. Gonadectomy and sex hormone treatment did not eliminate sex differences; overall, females had higher levels than males on measures of HPA function. Analyses of variance (ANOVA) indicated interactions of sex and sex hormone treatment on CBG levels and post-stress corticosterone levels in Expt. 1. The results suggest that sexual dimorphisms influence HPA function even when males and females are given equivalent physiological doses of gonadal steroids, and that the relevant sexual dimorphisms involve both the periphery and the CNS.     

The role of endocrines in isolation-induced lntermale fighting in albino laboratory mice. II. Sex steroid influences in aggressive mice

Isolation-induced intermale fighting in laboratory mice can be dramatically reduced under most circumstances by castration. This behavior in castrates may, however, be restored, or even accentuated, by androgen replacement. Experiments on the effects of sex steroids on such fighting in castrated mice, which, for want of a better term, are designated as “aggressive,” have been recently described. These mice are housed with a female until 10 days after siring a litter and are, thereafter, housed individually for a further 14 days before castration and subsequent hormone treatment. Such mice show substantial levels of fighting in “standard-opponent” tests even before isolation. Although castration results in reduced fighting in these mice, this behavior is rarely completely abolished in all individuals. It seems likely that steroid treatment of aggressive mice maintains or intensifies an already present motivation. Treatments in these studies consisted of daily oil-based intramuscular injections for 14 days preceding and throughout behavioral testing. The standard-opponent tests were 7 min encounters with adult, subordinate, grouped males in the cleaned home cages of experimental mice. The steroids investigated included estradiol benzoate (EB), 19-hydroxytestosterone (19-OHT), androstenedione (A), testosterone (T), and Sα-dihydrotestosterone (DHT), either singly or in combination. The results suggest that (a) on a dosage basis, estrogens were at least as effective as androgens in maintaining fighting in castrated aggressive mice; (b) 19-OHT (one of the metabolic intermediates between testosterone and 17 β-estradiol) was also effective but somewhat less so than the same dose of EB; (c) the three naturally occurring androgens investigated all effectively maintained fighting at comparatively low doses (50 μg/day) which compares with a replacement dose of 500 μg/day of T in some studies in traditional castrated mice (e.g., Luttge and Hall, 1973); (d) aromatization is not essential for a behavioral action of androgens as DHT, a nonaromatizable androgen, maintained fighting in these mice; (e) whereas a two-site (central motivational and peripheral penile) action seems probable in the influence of androgens on sexual behavior in castrated rats (e.g., Parrott, 1975), DHT did not augment the action of EB on fighting in castrated aggressive mice, indicating that only a central action of steroids was required in the aggressor.     

The relationship between aggressive and sexual behavior in male mice: Effects of testosterone and parachlorophenylalanine

The purpose of this study was to clarify the connection between aggressive and sexual behavior with the aid of testosterone propionate (TP) and parachlorophenylalanine (PCPA). Previous studies have indicated that aggressive and sexual behavior are positively correlated, and it has been suggested that both behaviors are related to the level of general arousal. Testosterone has documented effects on both aggressive and sexual behavior. It has been hypothesized that these effects are due to an increased level of general arousal. If this is the case, aggressive and sexual behavior could be restored by administration of drugs excitating the central nervous system, e.g., PCPA. The present study examined the effects of TP and PCPA on aggressive and sexual behavior in gonadectomized male mice. Control animals were injected with sesame seed oil or saline. The level of aggressiveness was assessed by means of dyadic tests with gonad-intact male opponents. For the sexuality tests, a receptive female was placed in the home cage of the experimental male. The results showed that male mice injected with PCPA were more aggressive than the males of the other groups, while the TP-exposed males expressed the most sexual activity. Compared to the control group, the PCPA and TP groups were more active in both the aggression and the sexuality tests. These findings lend support to the hypothesis that the earlier documented correlations between aggressive and sexual behavior could be due to both behaviors being dependent on a certain level of general activation. Aggr. Behav. 24:367–377, 1998. © 1998 Wiley-Liss, Inc.     

Role of neonatal androgens in sexual differentiation of brain structure, scent marking, and gonadotropin secretion in gerbils

Gerbils display a sexually dimorphic scent marking behavior that responds to testosterone (T) in adulthood and develops under the influence of testosterone perinatally. A complex of cell groups between the preoptic area and anterior hypothalamus of the gerbil brain is also sexually dimorphic and responsive to testosterone. One of these cell groups, the sexually dimorphic area pars compacta (SDApc), usually exists only in males. Even when given testosterone, adult female gerbils rarely have an SDApc. To determine if the SDApc develops under the influence of testosterone, male gerbils were castrated or given sham operations on the day they were born or 1 day later, or were not manipulated. Female gerbils were injected subcutaneously with 0, 50, or 100 micrograms testosterone propionate (TP) on the day after birth. When given ovarian transplants as adults, neonatally castrated males scent marked at low levels typical of females. Neonatally androgenized females given testosterone as adults scent marked at high levels typical of males. Neonatal castration did not affect the probability that the SDApc would develop, but neonatal androgenization did. Half the females given either dose of TP as neonates had SDApcs bilaterally. The sizes of the SDApcs present in females depended on the dose of testosterone given neonatally. The larger dose produced larger SDApcs. The 100-micrograms dose of TP also defeminized gonadotropin secretion, but the 50-micrograms dose did not. The castration of males neonatally prevented the defeminization normally caused by endogenous testosterone. Both groups of neonatally castrated males formed corpora lutea in their ovarian transplants, but control males did not.     

Evidence that a factor besides progesterone, prolactin, or plasma-estradiol-binding protein inhibits estrogen-induced sexual receptivity in pregnant rats.

Daily administration of estradiol benzoate stimulated significantly less lordotic behavior in rats during the second half of pregnancy than in ovariectomized females that received subcutaneous progesterone implants, pituitary grafts that raised plasma prolactin, or both treatments combined. Following an initial facilitation of receptivity, females with progesterone implants showed only moderate reductions in lordosis quotients over 3 test days. The capacity of plasma from pregnant rats to bind estradiol was found to increase significantly during the second half of pregnancy. However, daily administration to pregnant rats of a synthetic estrogen, R 2858, which is not bound by plasma protein, was no more effective than estradiol benzoate in stimulating receptive behavior. Administration of estradiol benzoate also stimulated significantly lower levels of sexual behavior in pregnant females than in females in which pseudopregnancy had been prolonged by previous hysterectomy or induction of uterine decidualization. These findings suggest that some endocrine factor other than progesterone, prolactin, or estradiol-binding protein is primarily responsible for the potent suppression of behavioral responsiveness to estrogen which occurs in pregnant rats. It is suggested that 5 alpha-reduced androgens may cause these behavioral effects.     

Sexual cycles in female dogs treated with androgen during development

This experiment was conducted to study hormonal and behavioral cycles in female dogs exposed to androgen during development. The four groups, each consisting of five subjects, were "Normal" females, "Prenatal" females exposed to testosterone propionate (TP) before birth, "Postnatal" females injected with TP for 3 months postpartum, and "Prepost" females exposed to TP in utero and again to testosterone for 4--6 weeks after birth. All Normal females had two estrous cycles during which they showed vaginal bleeding, ovulation, progesterone (P) secretion, sexual receptivity, and were attractive to males. All androgen-treated females showed at least 1 cycle with ovulation and P secretion. Three Postnatal females developed the delayed anovulatory syndrome. Genital bleeding through the vagina (Postnatal group), or through the "penis" (Prenatal and Prepost groups), occurred in 4 Postnatal, 3 Prenatal, and 1 Prepost female. Attractiveness for males was observed in all Prenatal and Postnatal females, but in no Prepost subject. Receptivity was present in four of five Prenatal females but not in any Postnatal or Prepost female. Occurrence of cycles in treated females indicated functional integrity and sensitivity to estrogen in brain mechanisms producing gonadotropin-releasing hormones. Absence of receptivity is referred to diminished responsiveness to ovarian hormones in brain mechanisms mediating receptive behavior. Absence of genital bleeding and lack of attractivity are due to lowered response to estrogen in uterine and vaginal epithelium which results in reduced extravasation of blood, and in failure to secrete the putative "pheromonal" agent normally responsible for attractiveness.     

Mesencephalic participation in the control of sexual behavior in the female rat

Electric stimuli applied to both pudendal nerves evoked field potentials, unit responses, and multiunit responses in the ventrolateral midbrain, in and around the peripeduncular nucleus. Bilateral lesions placed in this region suppressed sexual behavioral responses (lordosis and courting behavior) of ovariectomized rats primed with 5, 10, 100, and 1,000 microgram of estradiol benzoate and 2 mg of progesterone per kilogram of body weight. It is proposed that the region in question represents a relay station for the integration of sensory and endocrine information concerned in the control of receptive sexual behavior in the female rat.     

Analysis of the catnip reaction: mediation by olfactory system, not vomeronasal organ

Pet owners and behavioral scientists alike are fascinated by unique behavioral reactions that cats show in the presence of catnip. These experiments explored the possibility that the catnip reaction might be triggered by chemosensory stimulation of the vomeronasal organ. In the chewing and mouthing of the catnip source, substances might be dissolved in saliva and transported to the vomeronasal organ. The rolling and rubbing during a catnip reaction might be a sexual response activated by the accessory olfactory system since the system projects to parts of the brain involved in mediation of sexual behavior. However, removal of the vomeronasal organ did not attenuate any of the behavioral reactions to catnip. Olfactory bulbectomy immediately eliminated catnip responding, revealing that the chemosensory stimulus evoking the catnip reaction is undoubtedly mediated through the main olfactory system. Catnip activates behavioral elements associated with several species-specific behaviors, including sniffing and chewing as associated with oral appetitive behavior, rolling and rubbing characteristic of female sexual behavior, batting the catnip source characteristic of play behavior, and a type of kicking associated with predatory behavior. These behavioral reactions occur randomly and intermittently.     

Differential sexual activity of isolated and grouped male mice despite testosterone administration

In Experiment 1, adult male C57 mice were castrated, housed individually or in groups of four, and repeatedly injected with either of two doses of testosterone. Control mice were sham-castrated, individually or group housed, and injected with oil vehicle. In repeated tests of sexual behavior with receptive females, isolated males in all surgery-dose combinations showed significantly more mounts and intromissions than did their group-housed counterparts. Ejaculations were fully restored by testosterone in castrated grouped males but not in castrated isolated males. In Experiment 2, administration of either of two doses of testosterone failed to elevate the sexual behavior of intact group-housed males. These experiments show that housing with other males depresses all major measures of sexual behavior, and suggest that this is probably independent of testicular hormones.     

Male-female differences and the influence of neonatal and adult testosterone on intraspecies aggression in rats.

Male and female albino rats were tested for intraspecies aggression without the use of shock. In the first experiment, male pairs showed more biting attacks, offensive sideways movements, and self-grooming than did female pairs; male pairs also showed more stereotyped defensive/submissive behaviors and were wounded more frequently. The second experiment examined the effects of neonatal castration and testosterone propionate (TP) administration on fighting. Males castrated at birth attacked other males less frequently than did controls when tested with TP treatment as adults. The TP given at birth to neonatally castrated males restored attacks to control levels. Females given TP as neonates did not differ from either male or female controls. Other aggressive/defensive behaviors, however, did not show this pattern. The results suggest that while the presence of testosterone during a brief postnatal period and during adulthood is necessary for attack behavior to occur, other related behaviors may not be affected in a similar manner.