Differential hormonal control of aggression and sexual behavior in female Syrian hamsters

These experiments were designed to test the effects of chronic estradiol treatment on aggression and sexual behavior in female hamsters. Isolated female hamsters were ovariectomized and tested for their behavioral responses to a group-housed, ovariectomized female hamster (aggression test) and a group-housed, intact male hamster (sexual behavior test). Following these baseline tests, the experimental females were implanted sc with Silastic capsules containing different concentrations of estradiol (100, 25, 10, or 0%) diluted with cholesterol and retested 3, 7, 10, and 14 days after implantation. High levels of aggression were observed on the baseline test, with no changes in aggression toward an intruder female observed for any implant group on subsequent tests. Despite these high levels of aggression toward another female, most of the estradiol-treated females (80% at 14 days) were sexually responsive in the presence of a male. There was no effect of Silastic estradiol concentration on sexual behavior, even though a range of serum estradiol levels (39–105 pg/ml) resulted. Lordosis latencies decreased and lordosis durations increased over the extent of estradiol treatment. Seventeen days after Silastic implantation, all females were injected with progesterone and retested. Estradiol-treated females showed an extreme reduction in aggression toward a stimulus female, as well as a further stimulation of sexual behavior after progesterone treatment. High levels of aggression in cholesterol-treated females (0% estradiol) were maintained even after progesterone injection, and these females never displayed any sexual responsivity. These results suggest that sexual behavior in the female hamster is sensitive to estradiol alone, whereas the inhibition of aggression requires the combination of estradiol plus progesterone.     

Estradiol administration and the sexual activity of castrated male rhesus monkeys (Macaca mulatta)

To examine whether estradiol might be effective in maintaining sexual behavior after castration or after testosterone withdrawal, we have observed male rhesus monkeys during daily 1-hr tests alternately with each of two ovariectomized, estradiol-treated females (four males, four females, eight male-female pairs, 798 tests). Estradiol (2-5 micrograms/kg sc/day) or vehicle was administered in counterbalanced order immediately after castration and again immediately after withdrawal of testosterone propionate treatments (800 micrograms and 1.6 mg sc/day). There were no significant differences in behavior during vehicle and estradiol treatments to indicate that estradiol helped to maintain male sexual activity. Instead, estradiol treatment tended to interfere with the capacity to intromit. This supported the results of other studies, namely, that the systemic administration of estradiol does not enhance the sexual behavior of castrated male macaques, and raises questions about the role of both aromatization and estrogen receptors in the male primate brain.     

Adrenal contribution to the induction of sexual behavior in the female musk shrew.

Sexually experienced female musk shrews (Suncus murinus) lack an ovarian, vaginal, and behavioral estrous cycle. Females, once induced by their initial contact with a male, are able to display copulatory behavior whenever a male is present (Rissman, Silveira, and Bronson, 1988). Based on plasma levels of steroids, and on hormone replacement studies conducted after ovariectomy (OVX), we have shown that testosterone (T) plays an essential role in the regulation of female sexual behavior (Rissman and Crews, 1988; Rissman, Clendenon, and Krohmer, 1990a; Rissman, 1991). To date we have only examined the potential contribution of adrenal steroids to female sexual behavior in a preliminary manner. After adrenalectomy, gonadally intact females display significantly lower levels of sexual behavior than controls (Rissman and Bronson, 1987). The following experiments were conducted to examine the role the adrenal steroids (in contrast to the medullary hormones) play in the induction of female sexual behavior in the musk shrew. In the first experiment gonadally intact females were treated with dexamethasone (DEX) to reduce the secretion of adrenal steroids. Significantly fewer females receiving DEX demonstrated sexual behavior as compared with controls. In the second study, OVX females received T-filled Silastic implants. When DEX was administered to OVX + T females at a dose that dropped circulating T levels to those found in ovary and adrenal intact females, no effect on sexual behavior was noted. The data show that the adrenals are a behaviorally important source of T and contribute toward the hormonal control of sexual behavior in these female mammals.     

Sexual behavior in developing male rats

During normal development, the onset of reproductive behavior in male rats was not preceded by any change in plasma testosterone (T) levels. Implantation of Silastic capsules containing T in 14-day-old male rats advanced the onset of all parameters of sexual behavior by 20 days. Implantation of Silastic capsules containing estradiol in 14-day-old male rats stimulated precocious mounting and intromitting, but not ejaculation. Implantation of dihydrotestosterone-filled Silastic capsules in 14-day-old male rats completely inhibited the development of sexual behavior. All hormones suppressed plasma LH levels. These findings in immature male rats are similar to previous findings in adult males. Immature male rats were behaviorally less responsive to T than adult males, and it was suggested that, during development, male rats become progressively more sensitive to the behavior-stimulating effects of circulating T. No effects of copulatory experience on plasma concentration of T or on the weights of testes, penes, or accessory sexual glands were detected.     

Heterosexual interactions in laboratory-housed stumptail macaques (Macaca arctoides): observations during the menstrual cycle and after ovariectomy.

Heterosexual interactions of pairs of stumptail macaques (Macaca arctoides) were studied in relation to the female menstrual cycle and after ovariectomy. Five intact male and 10 tubal-ligated female macaques were observed in laboratory pair tests of 20-mins duration, and data were obtained on various male and female behaviors. Each male was tested with the same two females during four 40-day observation periods. Males were tested daily and females were tested every other day. After two 40-day testing periods, one female partner of each male was ovariectomized and the other was sham-operated. Blood was collected regularly from the females during the course of observation and serum levels of estradiol and progesterone were determined by radioimmunoassay. The midcycle peak of estradiol was observed to occur approximately 18 days prior to menses. A distinct secondary peak in estradiol was observed to occur during the luteal phase of all cycles examined. Of 28 different male and female behaviors studied only female presentation to male sexual contact showed a significant midcycle peak related to the endogenous estradiol surge. After ovariectomy a significant decrease in the frequency of several male copulatory behaviors was observed, but most males continued to copulate regularly with their spayed partners throughout the period of this study. Thus, the pattern of copulatory behavior observed in stumptail macaques over the cycle of the female partner and subsequent to ovariectomy differs from that observed in other macaque species studied in the laboratory. It is concluded that cyclical fluctuations in the level of ovarian hormones are not significantly related to measures of sexual interactions in laboratory tests of this species, although the maintenance of copulation and associated behaviors at high levels depends to some degree upon the ovary.     

Continued copulation of ovariectomized adrenal-suppressed stumptail macaques (Macaca arctoides).

Female stumptail macaques continue to copulate at moderate to high levels for years after gonadectomy. This study examined the extent to which sexual behavior of ovariectomized stumptail females was maintained by steroids of adrenal origin, and second, considered the possibility that ovarian fragments might have been left in situ following surgery. Daily injections of 0.1 mg of dexamethasone sodium phosphate suppressed serum cortisol, estradiol, and testosterone by at least 85% in three of four ovariectomized females, but dihydrotestosterone was suppressed by only 50 to 70%. The fourth female showed maximal suppression of cortisol but maintained much higher levels of the other steroids, in particular estradiol, and therefore it was strongly suspected that this animal had an ovarian fragment.Within the limits to which sex steroids were depressed with dexamethasone, no correlation was found between steroid levels and sexual performance. Ejaculatory frequencies and measures of attractivity, proceptivity, and receptivity collected during heterosexual pair tests remained unaffected in all four females during 4 weeks of dexamethasone treatment. Thus it was concluded that the maintenance of copulatory activity after ovariectomy in this species was largely due to nonsteroidal mechanisms.     

Exposure to developing females induces polyuria, polydipsia, and altered urinary levels of creatinine, 17β-estradiol, and testosterone in adult male mice (Mus musculus)

Novel male mice can accelerate reproductive maturation in proximal developing females, an effect mediated by the chemistry of the males' urine. Exogenous estrogens can similarly accelerate female sexual development. In Experiment 1, adult male mice were housed across wire grid from either empty compartments or those containing post-weanling females. Proximity of females caused males to urinate more, progressively over days of exposure, with most urination directed towards females' compartments. Male urine collected after 5 days in these conditions was analyzed by enzyme immunoassay for 17β-estradiol, testosterone, and creatinine. Urinary creatinine of isolated males significantly exceeded that of female-exposed males. Unadjusted urinary steroids also trended toward higher levels in isolates, but creatinine-adjusted estradiol and testosterone of female-exposed males significantly exceeded that of isolated males. In Experiment 2, measurement of water consumption indicated significantly greater drinking by female-exposed as opposed to isolated males. In Experiment 3, males were housed in isolation or beside post-weanling intact (sham-operated) females, ovariectomized females, or intact (sham-operated) males. Male water consumption was elevated in all conditions involving social contact. Urinary creatinine was significantly lower in female-exposed males compared to isolated controls, while unadjusted testosterone was significantly lower in males in all social conditions. Again, creatinine-adjusted estradiol in female-exposed males significantly exceeded that of isolates. These data indicate that adult males drink and urinate more, have more dilute urine, and have a higher ratio of estradiol to creatinine when they are near developing females. These dynamics increase females' exposure to urinary steroids and other urinary constituents that can hasten sexual maturity.     

Sex differences in odor-stimulated flank marking in the golden hamster (Mesocricetus auratus).

To determine whether sex differences exist in the frequency of odor-stimulated flank marking, intact male and female hamsters were exposed to the recently vacated home cages of male stimulus hamsters for a 10-min test on 4 consecutive days. Females were found to mark at significantly higher levels than males. To investigate the role of gonadal hormones in the sex differences in flank marking, gonadectomized male and female hamsters were implanted with Silastic capsules containing estradiol or testosterone. Females exhibited twofold higher levels of odor-stimulated flank marking than males, and the amount of flank marking was significantly higher when the hamsters were administered testosterone than when they were administered estradiol. These data demonstrate that sex differences exist in the frequency of flank marking stimulated by the odors of male hamsters, and that these sex differences do not appear to result from the typical sex-specific patterns of circulating levels of estradiol and testosterone.     

A prenatal source for defeminization of female rats is the maternal ovary

Sexual behavior in laboratory rats is influenced by a variety of factors in the perinatal environment. Male rats are masculinized and defeminized in response to circulating testosterone perinatally. Females undergo a process of feminization but in some cases are exposed to testosterone. Previous work has shown that during prenatal development female rats normally undergo a partial masculinization and defeminization of sexual behavior as reflected by altered responsiveness to gonadal hormones in adulthood. In the present study we investigated whether the maternal ovary influences adult females' responsiveness to gonadal hormones. Pregnant rats were ovariectomized on Day 10 of pregnancy and their offspring tested for sexual behavior in adulthood. Following ovariectomy pregnancies were maintained by administration of systemic progesterone. In addition the ovariectomized pregnant rats were given one of three daily treatments (Days 10-21): 0.2 microgram estradiol benzoate in sesame oil and 0.1 cc propylene glycol, 5 mg of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) in 0.1 cc propylene glycol, or 0.1 cc propylene glycol. A control group was generated from SHAM operated mothers given daily control injections of propylene glycol and sesame oil. Offspring were ovariectomized in adulthood and tested for display of feminine sexual behavior in response to estradiol benzoate and progesterone or estradiol benzoate alone. Masculine sexual behavior was measured in response to testosterone propionate (TP). Feminine sexual behavior was enhanced in offspring from ovariectomized mothers given only progesterone replacement during pregnancy. Offspring from mothers treated with ATD displayed the greatest elevations in feminine sexual behavior. Estradiol treatments of ovariectomized mothers prevented the increase in feminine potential seen in offspring in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anabolic-Androgenic Steroid Effects on Sexual Receptivity in Ovariectomized Rats

Anabolic-androgenic steroid (AAS) compounds are synthetic androgens taken by athletes to increase physical strength and endurance. Recent studies in our laboratory have demonstrated that AAS administration disrupts the estrous cycle of Long–Evans rats. The present experiments examined the effects of six commonly abused AAS compounds on sexual receptivity in ovariectomized rats. Adult female Long–Evans rats received estradiol benzoate (EB; 2.0 μg/day sc) for 6 consecutive days followed by 15 days of EB concurrent with daily sc injections of 7.5 mg/kg of one of the following AAS compounds: 17α-methyltestosterone, methandrostenolone, nandrolone decanoate, stanozolol, oxymetholone, testosterone cypionate, or the oil vehicle. On Day 15, all female rats received progesterone (1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of AAS treatment. Although the time course of AAS effects on sexual receptivity varied, some overall effects were clear. For example, 17α-methyltestosterone, methandrostenolone, nandrolone decanoate, and stanozolol interfered with the display of sexual receptivity on Day 14, whereas oxymetholone and testosterone cypionate had no effect. Rats in all groups displayed high levels of sexual receptivity after receiving progesterone on Day 15. Our results show that AAS compounds vary in their degree of inhibition of female sexual behavior in ovariectomized rats.     

Preference for an estrous female over a non-estrous female evinced by female rats requires dihydrotestosterone plus estradiol

The effects were studied of long-term treatment with testosterone metabolites (dihydrotestosterone, DHT, and estradiol, E2, in sc Silastic implants) on preference behavior of ovariectomized female rats for an estrous female over a non-estrous female. For measuring this behavior a residential plus-maze was used which harbored two ovariectomized “stimulus” females on the top of peripheral boxes, one of which was made estrus by injection of estradiol benzoate and progesterone. When both steroids (DHT plus E2) were circulating simultaneously they evoked preference for an estrous female, while neither steroid by itself sufficed. In earlier work with adult male rats castrated on the day of birth, E2 was effective in the absence of DHT. This sex difference, therefore, seems to have arisen before birth. Further, administration of DHT alone caused a profound lack of interest in both “stimulus” females, which cannot be fully explained by the reduced locomotor activity which has been found to be induced by DHT in earlier Studies.     

Studies on the possible role of 2-OH-estradiol in the control of sexual behavior in female rats

$\text{In vitro}$ studies have revealed that 2-OH-estradiol can be produced in the brain and that it can compete with estradiol for hypothalamic cytosol binding sites. In the present study ovariectomized female rats received 2-OH-estradiol via sc or iv injections and/or via direct intracerebral implantation either alone or in combination with vehicles, estradiol or testosterone. Behavioral tests after sc progesterone priming indicated that 2-OH-estradiol has relatively weak estrogenic, and no apparent anti-estrogenic or antiaromatization activity in the induction of sexual receptivity.     

Steroid hormone influences on the mating behavior of vervet monkeys (Cercopithecus aethiops)

Eight ovariectomized female vervet monkeys (Cercopithecus aethiops) were tested in heterosexual and isosexual pairs, under estradiol and testosterone treatments. Pairs were tested under two different experimental situations in which the male was either restrained or left free. There were only small behavioral changes across the treatments, involving mainly male responses. Erection time, frequency of intromission, ejaculation, and olfactory investigation increased during estradiol treatment whereas during administration of testosterone erection time, the number of approaches, contacts, and olfactory investigations decreased. Female behaviors were relatively independent of hormone treatment showing only the disappearance of negative responses with estradiol and an increase of yawns with testosterone. Female behaviors were performed at a higher level with male partners than with other females, and the frequencies of spontaneous presents varied with the sex of partner. It is suggested that in vervet monkeys both estradiol and testosterone affect female attractivity, estradiol further influences receptivity, whereas proceptivity appears to be less directly involved in sexual interactions and more related to social context.     

Sexual behavior and scent marking in male gerbils: comparison of changes after castration and testosterone replacement

This study compared changes in sexual behavior of male gerbils with changes in scent-marking frequency following castration and exposure to various doses of testosterone. Castration eliminated sexual activity in male gerbils. Injections of testosterone propionate (75 μg twice weekly) prevented this decrease. Larger (600 μg) injections of testosterone propionate or implantation of Silastic capsules of testosterone reinstated mating behavior. Sexual behavior showed a different pattern of changes than scent marking. Sexual behavior was maintained more effectively than scent marking by hormone injections, but scent marking was reinstated more readily than sexual behavior by the tonic hormone levels produced by Silastic implants.     

Seasonal changes in reproductive behavior in two ovariectomized female rhesus monkeys treated year-round with estradiol

Two ovariectomized female rhesus monkeys treated year-round with estradiol-filled capsules were used in hour-long behavioral tests with male rhesus monkeys both in and out of the normal breeding season. The study was designed primarily to test male hormonal responses to copulatory behavior and it was expected that behavior of the females would be essentially the same under both seasonal conditions. Several behaviors of the female, however, were found to fluctuate on a seasonal basis, namely (1) proximity to the male, (2) grooming of the male, (3) sexual presentations, and (4) threatening away (a form of sexual invitation). All of these behaviors, except proximity, were found to be positively correlated with the male partner's testosterone levels before and after the behavior test in the only test condition in which most males ejaculated. The preliminary suggestion is made that these females responded to some cue, either from the environment or from the males, that caused a change in their behavior between breeding and nonbreeding seasons despite the constant hormonal environment provided by the estradiol capsules. Since the same behaviors which were sensitive to seasonal effects were positively correlated with male testosterone levels, it is possible that the male's hormonal status affects affects female behavior.     

Effects of ovarian hormones on the behavior of captive Macaca fascicularis

To examine the effects of ovarian hormones on the behavior of female Macaca fascicularis and their male partners, daily 1-hr behavior tests were conducted while ovariectomized females were (1) untreated, (2) given estradiol benzoate (EB) (5 μg subcutaneously [s.c.]/day), (3) given estradiol benzoate together with increasing doses of progesterone (P) (5 mg, 10 mg, and 20 mg. s.c./day), and (4) given testosterone propionate (TP) (0.25 mg s.c./day) (six pairs, 540 tests). Weekly blood samples were analyzed by radioimmunoassay for plasma hormone levels (81 samples). Estrogen treatment produced plasma estradiol levels similar to those of intact females during the late follicular phase of the menstrual cycle. Additional progesterone at the lowest dose produced plasma progesterone levels similar to or somewhat higher than those during the midluteal phase, while higher doses produced supraphysiological levels. Androgen treatment resulted in plasma levels well above the physiological range. Hormone treatments produced highly significant effects on the sexual, social, and aggressive interactions of the pairs. As in rhesus monkeys, estrogen increased male and female sexual activity, and increasing doses of additional progesterone reversed these effects. Unlike in rhesus monkeys, testosterone propionate increased both female sexual motivation (invitations) and also male sexual activity and ejaculatory performance. The direction of the hormone-dependent changes in grooming and aggressive interactions confirmed earlier results with intact females and indicated that aggressive interactions and male grooming times were highest, and female grooming times were lowest, when copulatory activity was at its height.     

Testosterone propionate treatment of an XY gonadal dysgenetic chacma baboon

Behavioral studies of an XY gonadal dysgenetic chacma baboon prior to and during testosterone propionate treatment were carried out. The orchidectomized dysgenetic individual, two intact males, a castrate male, and two ovariectomized females were pair-tested with a group of eight ovariectomized stimulus females prior to and during their treatment with estradiol benzoate. Three test series were carried out. One series occurred prior to any treatment of the agonadal focal subject animals. During this series it was only the intact males who showed behavior change during their testing with the estrogen treated females. A second test series occurred after a month of daily testosterone propionate injections (1 mg/kg/day) had been given to the four agonadal subjects. During this test series the castrate male ejaculated once with one of the estrogen-treated females. All of the treated subjects showed increases in their frequency of yawning. Upon completion of this test series the androgen dosage was increased (2 mg/kg/day) and 2 weeks later a third test series was carried out. During this series the castrate male ejaculated with five of his eight estrogen-treated partners. The yawning of all the treated subjects continued. As had been the case in the second series the XY gonadal dysgenetic individual continued to behave as did the ovariectomized females. None of these animals showed any increase in any measure of male sexual behavior. This study establishes the fact that a genetic male primate deprived of in utero exposure to testicular hormones will go on to develop as a normal genetic female and will fail to exhibit increased levels of male sexual behavior during androgen treatment.     

Cues that Elicit Ultrasounds from Adult Male Mice

Adult male mice (Mus musculus) which have a prior history ofexperience with other adult male and adult female mice readilyproduce 70 kHz ultrasonic vocalizations in the presence of urinefrom adult females but not in the presence of urine from adultmales. Urine from immatures of either sex does not elicit ultrasoundsfrom socially experienced adult males. The ultrasound elicitingpotency of adult male urine was not improved substantially followingcastration of adult males, injection of testosterone propionateto castrated adult males, administration of estradiol benzoateto castrated adult males, or neonatal castration. Ovarian hormonesdo not appear to be necessary for either the appearance at puberty,or the maintenance during adulthood, of the ultrasound elicitingcues of female urine. Stage of estrus did not have a major modulatingeffect on urinary cues eliciling male ultrasounds. Treatmentsthat did not substantially reduce the signal value of adultfemale urine include ovariectomy before or after puberty, ovariectomywith adrenalectomy, and neonatal administration of testosterone.The administration of testosterone to ovariectomized adult females,and hypophyseclomy, virtually eliminated the ability of urinefrom adult females to elicit ultrasounds from socially experiencedadult males. The implication of pituitary hormones in the modulationof female urinary cues thai elicit ultrasounds is particularlyinteresting since pituitary factors are also implicated in theproximal causation of postparturient maternal aggression, whichadult male ultrasounds may function to moderate.     

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.     

Deterioration of male sexual behavior in rats by the new prolactin-secreting tumor 7315b

The effects of hyperprolactinemia on male copulatory behavior in adult male and female rats were studied. Hyperprolactinemia was induced by the transplantable purely prolactin-secreting tumor 7315b. Male rats were castrated and received testosterone-filled capsules of different sizes which induced normal and subnormal testosterone levels. After sexual training the rats of the experimental groups were inoculated with tumor 7315b. Three weeks after tumor-inoculation high prolactin levels (2000-30000 ng/ml) were found. During this hyperprolactinemia ejaculation latency increased significantly, while the mount frequency and intromission frequency remained unchanged. Only 9 out of 22 rats ejaculated 19 days after inoculation. Moreover, it appeared that the inhibitory effect of the tumor was as strong in the presence of normal (2.33 +/- 0.07 ng/ml) as in the presence of low (0.35 +/- 0.01 ng/ml) testosterone levels. The inhibitory effect of tumor 7315b on copulatory behavior was not influenced by adrenalectomy. In gonadectomized female rats bearing testosterone-filled capsules tumor 7315b induced prolactin levels of about 2000 ng/ml and an almost complete cessation of mounts and intromission patterns 4 weeks after tumor-inoculation. It was concluded that tumor 7315b causes a strong inhibitory effect on male copulatory behavior in male and female rats and that this effect is not influenced by the presence of normal or low testosterone levels or removal of the adrenals, suggesting a direct effect of prolactin on brain functions.