Estradiol benzoate treatment of an XY gonadal dysgenetic chacma baboon

Behavioral studies of an XY gonadal dysgenetic chacma baboon under estradiol benzoate treatment were carried out. The dysgenetic individual and two ovariectomized conspecific control females were given a total of three testing series. The dysgenetic individual showed progressive success in her sexual interactions with her male partners and during her third testing series she was copulated with to ejaculation by five of the eight male partners. This study provides the first supportive evidence from a nonhuman primate for the predicted development of female sexual behavior in a genetic male deprived of testes prior to the sensitive period for sexual differentiation.     

The social interactions of adult conspecifics with an adult XY gonadal dysgenetic chacma baboon (Papio ursinus)

Two separate behavioral studies on an XY gonadal dysgenetic chacma baboon were carried out. In the first experiment the focal subject was treated identically as the control females by her adult male test partners. In contrast to the controls in this experiment the dysgenetic animal reciprocated the agonistic behaviors directed by the males toward her. In the second study intact and castrated males as well as ovariectomized females served as controls for the dysgenetic subject in tests with ovariectomized adult females. The stimulus females presented more to both classes of males than either the subject females or the gonadal dysgenetic individual, suggesting that the focal subject was treated by other female conspecifics as a female.     

Hormonal differentiation of sexual behavior in Japanese quail

The effect of hormones on the development of Japanese quail during the postembryonic period was examined. First, subcutaneous implants of estradiol monobenzoate (EB) and testosterone propionate (TP) were implanted 6–12 hr after hatching. EB and TP had no effect on the differentiation of sexual behavior in genetic males or females. However, EB had marked feminizing effects on plumage in genetic males. Second, the role of gonadal hormones during development was examined by gonadectomizing males and females 6–12 hr after hatching and treating them intramuscularly with EB or TP as adults. EB-treated adult females displayed sexual behavior typical of the genetic female and developed female plumage. A significant proportion of TP-treated females (57%) displayed male sexual behavior patterns. Cloacal gland development and male-type vocalizations were induced. EB-treated males displayed either male or female sexual patterns depending on the stimulus conditions. Third, to test whether bisexuality in gonadectomized males and females is maintained despite steroid treatment and expression of sexual behavior in adulthood, gonadectomized quail which were originally treated with EB received TP and vice versa. The results indicate that in the absence of gonadal hormones after hatching female quail remain bisexual until exposed to estrogen, whereas gonadectomized male quail retain behavioral bisexuality irrespective of prior estrogen or androgen exposure.     

Threshold for behavioral response to testosterone in old castrated male rhesus macaques

The sexual behaviors of old, intact (N = 5) and old, castrated (N = 6) rhesus macaque males were compared in six series of pair tests with receptive females. The castrated monkeys were tested when untreated and when given five doses of testosterone propionate (TP; 0.004, 0.016, 0.064, 0.256, and 1.024 mg/kg of body weight) in consecutive months. The serum testosterone (T) level was determined for each male before and after each series of tests. When untreated, none of the castrated males ejaculated, and yawning was significantly less in these monkeys than in intact males-no other behavioral measures differed significantly. Within 2 weeks of daily injections of 0.004 mg of TP/kg, two males ejaculated, and all differences in measures of ejaculation were eliminated. A third male ejaculated after 1 week of treatment with 0.016 mg of TP/kg. Yawning values did not differ during and after treatment with 0.064 mg of TP/kg. Although final mean serum T levels were six times higher in castrated (24.3 ng/ml) than in intact males (4.2 ng/ml), sexual performance levels did not exceed those of intact males.     

The role of neonatal androgen in the expression of hormonally induced maternal responsiveness in the adult rat

The role of neonatal androgen in the expression of hormonally induced maternal responsiveness in rats was investigated. Four to six hours postnatally male rats were either castrated or sham-castrated, while females were injected with testosterone propionate or oil, or were noninjected controls. When 90 days old the subjects were assigned either to a 21-day maternal hormone or to a vehicle regimen. Following these adult treatments subjects were tested for maternal responsiveness by means of a retrieving test in the home cage and in a T-maze. In the home cage test the adult hormone treatment caused a significant reduction in the time to sensitization in all neonatal treatment groups. In the T-maze only subjects with no androgen postnatally and with hormones in adulthood retrieved significantly more than their adult vehicle controls. It was concluded that the development of the potential to respond fully to the hormonal changes of pregnancy is inhibited by the postnatal presence of the male gonadal hormone.     

Testosterone-induced aggression in adult female mice

Silastic implants of testosterone (T) and injections of testosterone propionate (TP) were used to study the effects of ovariectomy and androgen administration on the fighting behavior of adult female mice. A dose of T previously shown to hyperstimulate accessory organ growth in adult male castrates was sufficient to induce the complete behavioral repertoire of male-like aggression in females never before treated with exogenous androgen. As determined by radioimmunoassay, blood levels of T produced by implants containing an aggression-inducing dose of T (10-mg implant) were within the range of T concentrations observed in intact males. Following treatment with a 10-mg T implant, the aggressive behavior of ovariectomized females could be fully maintained with a dose of T (0.3-mg implant) that failed to maintain weight of the accessory organs in adult male castrates. In fact, females “androgenized” were subsequently more responsive to the aggression-activating properties of T than were males castrated after prenatal and perinatal androgen exposure.     

Low potency of intact male rhesus monkeys after long-term visual contact with their female partners

We have examined the possibility that prolonged visual contact between future sexual partners, in the absence of any direct sexual contact and mating activity, is sufficient to produce the familiar-female phenomenon and is associated loss of male potency. For 1 year, 32 intact, feral-reared male rhesus monkeys were housed so that 14 males were in constant visual contact with their four future testing females, and 18 of the males were without any visual contact with females. After 1 year, each male was then tested once with each ovariectomized, estrogen-treated female (128 tests). Males in the group having prolonged prior visual contact (group II) were significantly less potent than males without prior visual contact (group I), and this difference was not related to plasma testosterone levels, prior history, time since capture, or presumed age. Group II males had fewer ejaculations during tests and ejaculated with fewer partners, and this appeared to be because they required significantly more stimulation (mounting and thrusting) to reach ejaculation. The data suggested that the familiar-partner phenomenon was not restricted to the male and was associated with increased social affinity and decreased agonistic tension between partners. Under natural conditions, the phenomenon may encourage troop transfers and outbreeding, and in laboratory studies, prior visual contact between testing partners should be regarded as a potentially uncontrolled source of variation.     

Ejaculation by male rhesus as a function of the female partner

Nine adult male rhesus monkeys were given eight 10-min tests of sexual behavior with eight ovariectomized female rhesus pretreated with estradiol benzoate. Males differed significantly in the number of tests during which they ejaculated, and females differed in the frequency with which specific males ejaculated when tested with them. With phylogenetic increase in neocortex, pair compatibility may be as important as hormonal stimulation in regulating male sexual performance. If this is correct, the problem of understanding the determinants of primate sexual behavior becomes more formidable.     

The effects of early and late androgen treatments on the behavior of Sarotherodon mossambicus (Pisces: Cichlidae)

Groups of Sarotherodon mossambicus were treated with androgen by immersion or oral treatment at various stages of development. Fish were allowed to mature and the effects of treatment on gonadal and behavioral differentiation were examined. The effects of treatment on gonadal differentiation were assessed by determining the sex ratio for each group. Three treatments resulted in sex ratios significantly different from the 1:1 sex ratio obtained in untreated fish. Behavioral differences were detected between groups of males in three measures of territorial defense and aggression, and differences were detected between groups of females in two measures of male-female courtship interaction. A second experiment determined that early-treated females were more sensitive to a second androgen treatment later in life than females not exposed to androgen during development. A number of sex-reversed genetic females functioning as males were detected in two treatment groups with predominantly male sex ratios. There were no differences in the behavior of sex-reversed and non-sex-reversed male fish from the same treatment group. This study establishes that hormone treatments administered during development influence behavioral differentiation in a teleost.     

Induction of male sex behavior in ewes with silastic implants containing testosterone propionate

In the first of two experiments, ovariectomized ewes with silastic implants containing testosterone propionate had higher concentrations of plasma testosterone than ovariectomized ewes with silastic implants containing testosterone (4.0 +/- .2 vs .8 +/- .1 ng/ml). In the second experiment, one or two 10 cm silastic implants filled with testoster-one propionate increased concentrations of plasma testosterone and induced male sex behavior in ovariectomized ewes similar to plasma testosterone levels and male sex behavior in rams. The interval from initiation of the treatment to the first behavior test in which mounting was consistently observed was 14.4 +/- 2.9 days and once mounting behavior was consistently induced, the testosterone treated ewes mounted estrous ewes an average of 10.7 +/- 1.3 times during a 10-minute test.     

Social and hormonal influences on behavior of adult male, female, and pseudohermaphroditic rhesus monkeys

We previously demonstrated that in a simple pair test situation the expression of adult male sexual behavior by rhesus monkeys depends on both prenatal (organizational) and adult (activational) androgen exposure. In the present study we used a more complex social situation (trio tests) to evaluate the behavior of males, females, and female pseudohermaphrodites. In these trio tests, the experimental subjects were tested with two estrogenized stimulus females simultaneously. Sex differences in behavior were made apparent by this complex testing situation that could not have emerged in the pair test. Gonadectomized males and female pseudohermaphrodites, but not ovariectomized females that were concurrently receiving TP, exhibited increased male sexual behavior in trio tests compared to pair tests. In trio tests, the males and pseudohermaphrodites showed evidence of partner preference by interacting almost exclusively with one of the two stimulus females. These "preferred females" in turn were responsible for the majority of the proceptive behavior exhibited in these tests. Ovariectomized females rarely displayed male sexual behavior in either test situation. These results further support the hypothesis that prenatal androgen exposure predisposes monkeys to exhibit masculine behavior traits when they reach adulthood and are exposed to the activational influences of androgens.     

Inhibition of estrogen-activated sexual behavior by androgens

Experiments to determine the potential of androgen to inhibit estrogen-activated female sexual behavior in rats were conducted. Treatment with either testosterone propionate (0.8 or 1.6 mg/day) or dihydrotestosterone propionate (0.2, 0.4, or 0.8 mg/day) significantly reduced the incidence of lordosis in ovariectomized females receiving estradiol benzoate (1 microgram/day). A similar suppression of estrogen-activated lordosis by testosterone was observed in castrated male rats. Flutamide, an androgen-receptor blocker, prevented the inhibition of lordosis by testosterone in females, indicating that the interaction of testosterone or a metabolite with an androgen receptor may be an important feature of this inhibition. Furthermore, the ability of dihydrotestosterone to inhibit lordosis at lower doses than testosterone suggests that the conversion of testosterone to dihydrotestosterone may also be necessary. These experiments demonstrate the potential of testosterone to inhibit the occurrence of female sexual behavior in rats, in contrast to its established facilitative effect on this behavior.     

Sexual behavior and sexual orientation of the female rat after hormonal treatment during various stages of development

The amount of circulating sex steroids during Postnatal Days 30-90 was varied in normally developed and in androgenized female rats. The influence of these manipulations on sexual behavior and sexual orientation was investigated. Normally developed or neonatally androgenized females were ovariectomized and implanted with estradiol through Postnatal Days 30-90 or sham-implanted. The remaining subjects were left intact during that period. The hormonal condition during Postnatal Days 30-90 significantly affected the behavior of normally developed females, but affected the behavior of neonatally androgenized females only to minor extent. Estrogen implants in normally developed females enhanced masculine sexual responses and induced a female-directed sexual orientation. Feminine sexual responses were unaffected by this treatment. Sham-implanted, normally developed females showed a male-directed sexual orientation and fewer masculine sexual responses than subjects which were left intact during Postnatal Days 30-90. Neonatal androgen treatment in general resulted in elevated levels of masculine Neonatal androgen treatment in general resulted in elevated levels of masculine sexual responses, inhibited feminine sexual behavior, and facilitated a female-directed sexual orientation.     

Effects of neonatal gonadal steroids on adult CA3 pyramidal neuron dendritic morphology and spatial memory in rats

The hippocampus is implicated in spatial cognition, which is sexually dimorphic and developmentally sensitive to gonadal steroids. Previously we have shown a sex difference in CA3 pyramidal cell layer volume and neuronal soma size that was reversible with neonatal castration in males or prenatal treatment of females with either testosterone propionate (TP) or a nonaromatizable androgen, dihydrotestosterone propionate, but not estradiol benzoate, all of which correlated with adult water maze navigation. The present study further investigates developmental androgen sensitivity of CA3 pyramidal neurons by measuring dendritic morphology and its relation to adult spatial ability. Female rats were injected with TP on postnatal day (P) 3 and P5 or ovariectomized (OVX) on P2, and male rats were castrated on P2, with or without testosterone replacement (Cas+T). Sham surgery controls were also included. Animals were tested on a water maze in adulthood, sacrificed, and CA3 pyramidal neurons were Golgi-stained and reconstructed in three dimensions using a computer-interfaced morphometry system. High-androgen groups (control males, Cas+T, TP females) performed better in spatial navigation and exhibited CA3 neurons with longer dendrites, a larger number of dendritic branches, and volumes of influence compared to low-androgen groups (control females, castrated males, OVX). Collectively, these findings indicate that the critical time period for organizational effects of androgens on the CA3 pyramidal neurons includes both prenatal and postnatal life, during which time androgens regulate developmental events such as somal growth and neuronal differentiation, all of which significantly contribute to establishing the sex difference in adult spatial navigation.     

Hormonal control of sex differences in ultrasound production by hamsters

Male and female hamsters differ in the stimulus control of the ultrasounds they produce during courtship and mating. In particular, untreated males show greater increases in ultrasound rate after exposure to stimulus females than after contact with other males. Conversely, estrous females are more responsive to stimulus males than females. This sex difference reflects both organizational and activational effects of gonadal hormones. Thus, responses to early castration or treatment with testosterone propionate (TP), estradiol benzoate (EB), or dihydrotestosterone propionate suggest that the development of male-like patterns of ultrasound production is facilitated by perinatal exposure to aromatizable androgen. However, even neonatally feminized subjects will show male-like calling if tested during adult treatment with TP. In contrast, the same subjects respond like naturally estrous females during adult treatment with EB plus progesterone (P). The contrasting responses of neonatally feminized subjects to later TP and EB + P treatments suggest that female hamsters retain a greater capacity for heterotypical patterns of ultrasound production than do males. This obviously differs from the common observation of greater "bipotentiality" for mating behavior in males. In turn, this suggests that the mechanisms controlling sexual bipotentiality are specific to their target behaviors, yielding distinct patterns of hormonal control for at least ultrasound production and lordosis.     

Facilitatory effects of pituitary transplants on intraspecific aggression in female hamsters

To help clarify the relationship between prolactin (PRL) secretion and aggression in the hamster, the aggressiveness of ovariectomized females given two ectopically grafted pituitary glands was compared to that of ovariectomized control females which underwent a sham transplantation procedure. In a series of three neutral territory tests with male partners, female-initiated attacks, chasing, and fighting were more frequent in the pituitary-grafted group than in the controls. Male partners of pituitary-grafted females responded by exhibiting more submissive behavior than did males paired with control females. In a final test in which pituitary-grafted females were paired with control female partners, control females were found to be more submissive and less aggressive than experimentals despite a significant body weight advantage. These results demonstrate a facilitatory effect of pituitary transplantation on aggression which is independent of gonadal hormones. Because an association between heightened aggressiveness and reported elevations in PRL secretion is observed in pituitary-grafted females and in pregnant and lactating females, these findings lend further support to the hypothesis that PRL promotes aggression during the hamster reproductive cycle.     

Sex differences in adrenal function in the lizard Cnemidophorus sexlineatus: II. Responses to acute stress in the laboratory.

Circulating concentrations of plasma corticosterone and gonadal steroids were measured in intact and gonadectomized male and female lizards (Cnemidophorus sexlineatus) following acute stress (handling) in the laboratory. There was a significant increase in plasma corticosterone after stress. Whereas intact females exhibited greater concentrations of corticosterone relative to intact males, ovariectomized females exhibited lower concentrations of corticosterone relative to castrated males. In addition to sex differences in corticosterone responses to gonadectomy, progesterone was elevated by stress in both intact and ovariectomized females but not in males. Corticosterone adjusted for castration and handling in males was negatively correlated with the plasma androgen level. The adrenal responsiveness of males to acute stress may be attenuated by androgens presumably secreted by the testis. Not only does adrenal function influence reproduction, but adrenal responses differ between males and females, and appear to be influenced by the gonadal axis. The sex differences in adrenal responses to stress likely reflect different reproductive strategies and nutritional requirements of males and females during the breeding season.     

An ovarian regression syndrome in the platyfish, Xiphophorus maculatus

The highly inbred Coatzacoalcos (Cp) strain of the platyfish, Xiphophorus maculatus, was noted for a high percentage of infertile females (XX). The ovaries of approximately one-quarter of all females regress. The time of gonadal atrophy varied from before sexual maturation up to 11 months of age. The gonadotropic zone of the pituitary was hypertrophied in regressed females. Transplants of immature testes and ovarian tissue into the caudal musculature of regressed females and the subsequent maturation of the grafts demonstrated that the ovarian degeneration was not due to pituitary or hypothalamic malfunction or an autoimmune disease. The cause of the gonadal degeneration was apparently localized to the ovary itself. This phenomenon was never observed in males (XY). Regressed ovaries fell into two categories, designated types I and II, with all being characterized by the presence of ductlike structures which resembled male efferent ducts, lined by Sertoli cells. Type I ovaries bore a marked similarity to certain mammalian dysgenetic gonads, while type II ovaries contained many proliferating germ cells and could be compared to the human neoplasm termed gonadoblastoma. It is suggested that the physiological lesion responsible for the ovarian regression syndrome involves the processes that control the determination and differentiation of the germ cells similar to those found in human 46,XY gonadal dysgenesis.     

Evidence that sex chromosome genes affect sexual differentiation of female sexual behavior

Female receptivity including the immobile hormone-dependent lordosis posture is essential for successful reproduction in rodents. It is well documented that lordosis is organized during the perinatal period when the actions of androgens decrease the males' ability to display this behavior in adulthood. Conversely the absence of androgens, and the presence of low levels of prepubertal estrogens, preserve circuitry that regulates this behavior in females. The current study set out to determine whether sex chromosomal genes are involved in the differentiation of this behavior. An agonadal mouse model was used to test this hypothesis. The SF-1 gene (Nr5a1) is required for development of gonads and adrenal glands, and knockout mice are consequently not exposed to endogenous gonadal steroids. Thus contributions of sex chromosome genes can be disassociated from the actions of estrogens. Use of this model reveals a direct genetic contribution from sex chromosomes in the display of lordosis and other female-typical sexual behavior patterns. It is likely that the concentrations of gonadal steroids present during normal male development modify the actions of sex chromosome genes on the potential to display female sexual behavior.     

Existence of an ejaculatory-like reaction in ewes ovariectomized and treated with androgens in adulthood

The complete behavioral repertoire of male sexual activity can be observed during daily androgen treatment (testosterone propionate, 15 mg/day) of normal ewes ovariectomized as adults. This includes the ejaculatory pattern (deep thrust accompanied by a rapid backwards movement of the head) which is followed by a dramatic decrease in the frequency of sexual interactions, similar to the male's postejaculatory reduction of activity. However, the sexual performances of the genetic females remain lower than those of normal males in ejaculation latency, postejaculation latency, and mount/ejaculation ratio.