Effects of neonatal exposure to progesterone on sexual behavior of male and female rats

Lactating females received daily injections of progesterone or oil, and their offspring were gonadectomized in adulthood and tested for both musculine and feminine sexual behavior elicited by estrogen, progesterone, and testosterone regimens. Male offspring of progesterone treated females exhibited significant impairment of masculine behavior elicited by both estrogen and testosterone. Latency and frequency of mounts and intromissions of those males which did engage in sexual behavior were not significantly different for the two groups. There were nonsignificant trends toward demasculinization of progesterone treated females and feminization of progesterone treated males. Progesterone administered to estrogen primed males failed to facilitate lordosis. There were no progesterone related differences in body weight at any time nor in testis or accessory organ weights of males. The results of this experiment confirm our previous finding of reduced sexual competence of intact male rats exposed neonatally to moderately increased levels of progesterone, and indicate that this effect is not the result of diminished adult hormone levels. Neonatal exposure to progesterone appears to have minimal or no effect on feminine sexual behavior of rats.     

Effects of sex and hormonal status on astrocytic basic fibroblast growth factor-2 and tyrosine hydroxylase immunoreactivity after medial forebrain bundle 6-hydroxydopamine lesions of the midbrain dopamine neurons

We examined astrocytic basic fibroblast growth factor immunoreactivity (FGF-2-IR) and tyrosine hydroxylase immunoreactivity (TH-IR) in the cell-body region of midbrain dopaminergic neurons after unilateral infusions of the neurotoxin 6-hydroxydopamine into the medial forebrain bundle in male and female rats. In addition, to determine whether neonatal exposure to gonadal hormones has consequences on the expression of astrocytic FGF-2 and cell loss in response to injury in adulthood, we studied the effects of these lesions in adult male and female rats that had been exposed or not to testosterone in the neonatal period. In both males and females there was a progressive loss of TH-expressing cells that peaked 5 weeks after the lesions. Females showed less loss of TH-expressing cells than males, but this effect was not estrogen dependent. Lesions led to an increase in expression of astrocytic FGF-2 that was greater in males than in females. Finally, it was found that, regardless of genetic sex, rats exposed to testosterone neonatally showed greater astrocytic FGF-2 expression after lesions than those not exposed, and that among those not exposed to testosterone, estrogen treatment had a modest protective effect.Analysis of behavior and striatal dopamine content showed that the percent of striatal dopamine depletion 14 days after the lesion correlated with the amount of behavioral asymmetry displayed by animals on all tests conducted after lesioning. In groups killed 2 and 5 weeks after the lesion, the amount of behavioral asymmetry correlated with the percent loss of TH-IR cells and with the percent increase in FGF-2-IR cells in the midbrain. These relationships were not evident in groups killed 3 and 7 days after the lesion, possibly because the changes in the number of FGF-2- and TH-IR cells were not fully manifested.The present findings show that hormonal events early in life can alter the response of midbrain dopamine neurons to insult and injury in adult life and suggest that the slow degeneration of these neurons may release signals triggering a sustained activation of adjacent astrocytes which, in turn, may lead to induction of astrocytic FGF-2.     

Sensitivity of male, female, and androgenized female rats to testosterone during extinction of a conditioned taste aversion

Experiment 1 tested the hypothesis that male and female rats differ in the amount of testosterone (T) required to prolong extinction of a conditioned taste aversion. Gonadectomized male and female rats were implanted with empty or 30-, 60-, or 120-mm T-filled capsules. The males had slower extinction rates than females when both were implanted with 30-mm and 60-mm capsules but not when implanted with 120-mm capsules. The dimorphic sensitivity was not due to differences in plasma T levels: the levels for males and females were not different. Experiment 2 tested the hypothesis that the presence of T during the perinatal period results in a greater sensitivity to T in adulthood. Females exposed to T during the perinatal period showed prolonged extinction when given a 30-mm T-filled capsule as an adult, whereas unexposed females did not. These results support the hypothesis that the amount of T required to activate the prolonged extinction in an adult depends on perinatal exposure to T.     

Effects of early sex steroid hormone treatment on courtship behavior and sexual attractivity in the red-sided garter snake, Thamnophis sirtalis parietalis

Previous research has shown that exogenous androgen fails to elicit courtship (chin-rubbing) behavior in adult male or female red-sided garter snakes (Thamnophis sirtalis parietalis). However, gonadectomized and intact newborn male and female red-sided garter snakes given silastic capsules containing testosterone exhibit chin-rubbing behavior; gonadectomized and untreated animals do not show this behavior. Both males and females also exhibit chin-rubbing behavior when treated with testosterone as yearlings. Hibernation stimulates chin-rubbing behavior only in males that have received androgen treatment as a neonate or as a yearling. Previous research has also shown that adult females, but not adult males, are courted if given estrogen treatment. Both newborn males and females will elicit chin-rubbing behavior from adult males if given estrogen treatment, indicating production and release of an attractiveness pheromone characteristic of adult females. Male red-sided garter snake breed for the first time on emergence from their second hibernation, whereas females probably do not breed until their third year of life. These data suggest that in the red-sided garter snake, a species that exhibits a dissociated reproductive tactic, sex steroid hormones act to organize central nervous system mechanisms subserving courtship behavior such that temperature, and not hormonal, fluctuations activate sexual behavior in the adult organism.     

Neonatal bonadal hormones: effect on maternal and sexual behavior in the male rat

Neonatal exposure of rats to androgen results in alteration of adult sex behavior and gonadotropin release. Other sexually dimorphic adult behaviors have also been shown to be dependent, either in part or in full, upon exposure to androgen neonatally. The present study was conducted to determine the effect of neonatal androgens in organizing the brain of the male rat (Long-Evans strain) with regard to maternal behavior. The results indicate that males neonatally exposed to androgen exhibit poor maternal behavior as adults when compared to males castrated at birth and males receiving gonadotropin antiserum in infancy. The males castrated at birth and males receiving gonadotropin antiserum in infancy, when primed with estrogen and progesterone, showed high levels of female sexual behavior when compared to controls. In terms of male sex behavior, the control groups performed slightly better than the males castrated at birth and males receiving antisera in infancy. The results suggest that the neonatal pituitary gland has an indirect role in the process of sexual differentiation.     

Investigation of biochemical factors related to non-bothersome nocturnal urination

We investigated the factors related to nocturnal urination that was not considered bothersome by comparing various parameters between subjects who felt nocturnal urination as bothersome and those who did not. A total of 94 persons (50 males and 44 females) were enrolled. They urinated >or= once per night. Each subject's perception of nocturnal urination was examined, and the subjects were divided into a bothersome group and a non-bothersome group. Blood biochemical data and urinary condition were compared between the two groups and various subgroups. There were 60 subjects (56 +/- 17 years old) in the non-bothersome group, and 34 subjects (57 +/- 17 years old) in the bothersome group. The serum melatonin level was significantly lower and the total score of the International Prostatic Symptom Score questionnaire (IPSS) and the quality of life (QOL) score were significantly higher in the bothersome group than in the non-bothersome group. Among 50 subjects with nocturnal urination >or= twice per night, the serum melatonin level was also significantly lower and the QOL score was significantly higher in the bothersome group than in the non-bothersome group. In conclusion, nocturnal urination might be not considered bothersome when subjects maintain sufficient levels of melatonin.     

Neonatal testosterone administration, but not in utero contiguity to males, augments the display of male sexual behavior by testosterone-treated adult female mice

Male copulatory behavior of adult female mice given slow-release capsules of testosterone was examined in animals that developed in utero contiguous to two males (mFm) or to two females (fFf). Other females of unspecified uterine position which were injected with testosterone propionate on the day of birth as well as intact males also were examined. mFm and fFf females did not differ on any measure; latency to the first mount, number of mount bouts, number of mount bouts with genital thrusting. The perinatally androgenized females exhibited more mount bouts and more bouts accompanied by genital thrusting than did mFm and fFf subjects. The former also displayed more mount bouts with thrusting on the second pair of tests than males. Lastly, a greater proportion of perinatally androgenized females than mFm or fFf animals displayed male sexual behavior two weeks following removal of the testosterone-containing capsule.     

Neonatal hormone experience and adult lordosis and fighting in the golden hamster.

Androgenization by testicular secretions or exogenous testosterone propionate (TP treatments administered 24-48 hr post partum) suppressed sexual receptivity in the golden hamster. In response to prolonged adult estradiol benzoate (EB) treatment, gonadectomized normal females and neonatally castrated males exhibited significantly longer total lordosis durations than normal male or neonatally TP-treated (20 mug or 200 mug) females. These results suggest that one aspect of androgen-induced masculinization in the hamster involves reduced estrogen sensitivity. Responses to sequential EB followed by progesterone treatment were also lower in the androgenized groups. Neonatally castrated males did not differ significantly from normal females in their lordosis behavior. Irrespective of adult hormone treatment, androgenized animals fought more than normal females or neonatally castrated males. A genital mask was used to reduce sex differences in peripheral stimulation during testing.     

Aggression by a female rat cohabitating with a sterile male: termination of pseudopregnancy does not abolish aggression.

At the end of that time, each female was assessed for aggressiveness toward an unfamiliar female intruder once each week for 3 weeks. Those females displaying a high level of aggression had their male cagemate changed. For half of the females, the new male cagemate was a castrated male with a testosterone implant. For the other half, the new cagemate was a castrated male without a testosterone implant. Replacement males had been subjected to surgery 9 weeks previously. There were no differences in the aggressiveness of females of the two groups on any of 3 subsequent weekly tests of aggression. In a 3-h evaluation of male sexual behavior, none of the 9 castrated males without testosterone replacement displayed sexual activity with an estrogen/progesterone primed ovariectomized female, but 6 of 9 males with testosterone replacement did. Reanalysis of the aggression data comparing the females whose males had no testosterone replacement and females housed with the 6 males that were sexually active also revealed no differences in aggression over the 21-day test period. Since pseudopregnancy is known to last 13 days, these results indicate that the continuous presence of pseudopregnancy is not required for maintenance of aggression by a female cohabiting with a sterile male.     

Effects of neonatal castration and testosterone on the rat's pup-killing behavior and activity

A male rat will generally kill young rat pups that are placed with him whereas a female generally will not. Another sex difference is that females are usually more active than males in the open-field test. This set of experiments was designed to evaluate the role of testosterone induced sexual differentiation in the development of these behaviors. The first experiment established that the frequency of the killing response is not diminished by castrating males in adulthood. The second experiment found that male rats which were neonatally castrated killed in fewer instances as compared to controls. These animals also were more active in the open field. Experiment 3 used males which had been handled or not disturbed in infancy to introduce an emotionality difference. Handling had no effect upon pup-killing behavior; again those castrated in infancy killed less often than controls. In Experiment 4 castrations at 2, 10 or 15 days of age were equally effective in stopping pup killing by males. In Experiment 5 females were androgenized at 2 days of age;this reduced their adult open-field activity but did not increase their pup-killing.     

Effects of prenatal antiandrogen treatment on masculinization and defeminization of guinea pigs.

Gonadectomized (gdx) guinea pigs which had received the antiandrogen flutamide prenatally were tested for female-typical and male-typical sexual behavior in adulthood. In tests for lordosis behavior, gdx males and females were injected with estradiol benzoate and progesterone. Prenatally flutamide-treated females showed a longer mean lordosis response than control females. This was true whether they were given either a high or a low dose of EB. No male ever showed a lordosis response. In tests for male-typical sexual behavior, gdx adult males were treated with testosterone propionate and tested with stimulus females. The prenatally flutamide-treated males showed significantly decreased levels of ejaculation, a lower intromission rate and a decreased percentage of mounts which included pelvic thrusts, when compared to control males. Mount rate and rate of pericopulatory behavior did not differ between the flutamide and control males. The fact that prenatal administration of flutamide increased female-typical behavior in adult females suggests that the female guinea pig is normally partially defeminized by androgens in utero. The male guinea pig appears to be resilient to attempts to block defeminization with prenatal antiandrogens. However, some aspects of masculinization can be blocked.     

Influence of Androgen and Estrogen on Delayed Skin Test Reactivity to Candida albicans

Recipient adult male CFW mice were passively sensitized to candida delayed skin test reactivity with splenic lymphoid cells from candida-vaccinated donor females. In recipient adult males that had been bilaterally gonadectomized as weanlings, before passive sensitization, reactivity was less than in the unilaterally gonadectomized controls. Adult males bilaterally gonadectomized as weanlings were treated with gonadal hormones during passive sensitization. 17β-estradiol was found to decrease reactivity, whereas testosterone was found to increase reactivity. These data provide evidence that delayed skin test reactivity produced by female lymphoid cells is depressed by estrogen and is stimulated by androgen.     

Sex hormones differentially influence voluntary running activity, food intake and body weight in aging female and male rats

The aim of this study was to examine the longer-term effects of reduced gonadal hormones on food intake, food efficiency, voluntary running activity and body weight in mature male and female rats, compared to age-matched controls. We hypothesized that hormonal effects would differ for rats that were not rapidly growing and our results are consistent with this hypothesis. 6-8?month male and female rats were divided into four groups: Female and male control groups and a female and male experimental group. Control groups were intact for 46?weeks. Experimental groups were intact during Phase I (16?weeks), ovariectomized or orchidectomized during Phase II (20?weeks), and received estrogen or testosterone hormone replacement therapy (HRT) during the final Phase III (10?weeks). Food intake and running distance were monitored daily and body weight was recorded weekly for 46?weeks. Contrary to findings for young and growing animals, we did not observe a (1) stabilization of food intake in female rats following OVX, (2) loss of body weight with ORX in males, or (3) complete restoration of running activity in ORX males given testosterone, compared to females given estrogen. Feeding efficiency was not affected by aging in females or males. Loss of estrogen increased energy intake whereas reduced testosterone in males resulted in a negative energy balance. Findings suggest variable hormonal effects for aging male/female rats.     

Effects of adult or perinatal hormonal environment on ultradian rhythms in locomotor activity of laboratory LEW/Ztm rats

Four experiments were performed with male and female rats of the inbred strain LEW/Ztm maintained under a light-dark schedule of 12:12 hours. The animals were subject to castration (GOX) or ovariectomy (OVX), estradiol 17 beta-implantation (E2-capsules), and perinatal hormonal treatments with testosterone propionate (TP) and an androgen antagonist (cyproterone acetate, CA). Results indicated a difference in the locomotor activity pattern between the two sexes as a result of the endogenous estradiol levels of the adult animals. The activity pattern of male LEW rats was characterized by ultradian rhythms of 4 and 4.8 hr periods. The female LEW rats, on the other hand, generally exhibited a clear circadian activity pattern and no ultradian activity rhythms. Following ovariectomy, each of the females showed distinct ultradian rhythms. These disappeared after E2-implantation. Castration of adult males had no effect on the ultradian activity pattern. Implantation of E2-capsules resulted in a marked decrease of the ultradian activity components. Perinatal treatment of the males with an androgen antagonist (CA) did not appear to effect ultradian rhythms during adulthood. Females treated perinatally with testosterone showed a significant increase in the ultradian activity components. This effect is assumed to be due to low estrogen levels in these animals during adulthood. Our study supports the assumption that ultradian rhythms are a result of changes in the phase relationships between several circadian oscillators. The synchrony of these oscillations seems to be facilitated by estradiol.     

Intrauterine position influences anatomy and behavior in domestic rabbits

In several rodent species, the sexual differentiation of a female offspring is known to be affected in utero by the testosterone produced in adjacent male littermates. The aim of this study was to investigate the effect of male neighbors on the sexual differentiation in domestic rabbits. For this, the intrauterine position (IUP) of a female offspring from unilaterally ovariectomized, multiparous mothers was determined by their birth order. Depending on the sex of the adjacent fetuses, pups were divided into 4 groups: 1. Males. 2. 2 M females (females with 2 adjacent males), 1 M females (females with 1 male neighbor), and 0 M females (females with zero adjacent male). Pups' anogenital distance (AGD) was measured at birth and on Day 180 postpartum, when spontaneous chin marking activity was also measured. Our results revealed that AGD was a reliable indicator of sex as male pups had larger AGD than females, both at birth and later on. Adjacent male fetuses had significant effect: the more adjacent male fetuses females have had the longer AGD they possessed. AGD at birth was a good predictor of AGD and behavior of adults, as 2 M does showed the longest AGD and the highest chin marking activity among females. We concluded that, similarly to rodents, proximity to males in utero affects both anatomy and behavior in rabbits.     

Organizational and activational effects of gonadal steroid hormones on the EEG of male and female rats

To analyze organizational and activational effects of sex steroids on adult rat electroencephalographic activity (recorded at postnatal day 100), seven groups were included: males (48)-intact, neonatally or adult castrated; females (64)-intact, ovariectomized and exposed pre- or neonatally to testosterone propionate. In males, neonatal orchidectomy increased beta relative power, whereas both neonatal and adult castration reduced interparietal correlation. In females, prenatal testosterone administration produced higher theta absolute power; theta relative power was higher in all experimental groups, whereas beta1 and beta2 were decreased by prenatal and increased by neonatal virilization; prenatal virilization enhanced, while neonatal virilization and adult ovariectomy decreased interparietal correlation. These data indicate that females are more sensitive to early prenatal than to neonatal organizational effects of sex steroids, and some electroencephalographic features are feminized in castrated males and virilized in perinatally androgenized females.     

Uterine position and conditioned taste aversion

Three experiments were designed to determine the influence of uterine position on the performance of female rats in a conditioned taste aversion paradigm. The first and second experiments confirmed a differential behavioral response by males and females during acquisition and extinction of the conditioned taste aversion. However, no differences were found between females that had caudal male littermates in utero (MF) and females that had no caudal male littermates (FF). In the third experiment, in which testosterone was administered to females throughout testing, MF females showed an increased sensitivity to testosterone and a more prolonged rate of extinction than FF females. Exposure to testosterone during prenatal development heightened postnatal responsiveness to testosterone in female rats. The results are discussed in terms of the organizational and activational effects of testosterone on behavior in a conditioned taste aversion situation.     

Female sexual behavior in male rats: effect of hour of castration at birth

In the male rat, a dramatic increase in serum testosterone occurs during the first four hours of postnatal life. The experiments sought to determine whether such an increase would participate directly on the defeminization process. Newborn male rats were castrated either at 0 hr in utero (literally at the moment of birth) or at 6 or 12 hrs after birth. Some males were castrated at 0 hr in utero and injected at the time of surgery with 1 or 5 micrograms testosterone propionate (TP). At about 90 days of age, each animal was injected with estrogen and progesterone and tested for female sex behavior. Males castrated at 0 hr in utero displayed typical female sex behavior. Males castrated at 6 or 12 hrs after birth were less receptive than males castrated at 0 hr. Males castrated at 0 hr and injected with testosterone at this time almost never showed lordosis as adults after treatment with ovarian hormones. These results are consistent with the idea that the rapid elevation in serum testosterone which occurs shortly after birth suppresses the development of sexual behavior sensitivity to ovarian hormonal stimulation.     

Developmental and activational effects of sex hormones on the attractiveness of dog urine

Adult male dogs were exposed to urine from five types of experimental donors: females ovariohysterectomized as adults (FOA), females treated with testosterone in utero (FTU), females treated with testosterone in early infancy (FTI), females treated with testosterone in utero and in early infancy (FTUI), males castrated as adults (MCA); and also to control urine from intact stud males (SM). Urine was collected from the five experimental groups of donors during three phases of the experiment: (a) during a period of no hormone treatment (NH); (b) following treatment with estradiol (E); and (c) following treatment with testosterone (T). Intact males were given no hormonal treatment and served as subjects and urine donors. Subjects spent about the same amounts of time investigating control SM urine in all three phases. In the NH phase, the investigation times for the five experimental samples were significantly greater than that of the SM sample. However, there were no significant differences between the investigation times of the five samples. During the E phase, in comparison with the NH phase, the investigation times were greater for all experimental samples. The increase in attractiveness was significant for FOA and FTU urine. During the T phase, compared with the NH phase, the investigation times were less for four experimental samples (FTU, FTI, FTUI and MCA urine), and FTI, FTUI and MCA urine were no longer preferred to the SM control. However, the decrease in attractiveness was significant for MCA urine only.     

Characterization of 50-kHz ultrasonic vocalizations in male and female rats

Male and female rats emit ultrasonic vocalizations in reproductive encounters. While estrous bedding has been used to elicit vocalizations of males, the number of responses is variable. We report a reliable method to assess vocalizations using exposure to a stimulus animal. The stimulus rat is placed behind a wire barrier for 5 min, then removed. Vocalizations are then recorded for 5 min. Experiment 1 validated this method and it was used for subsequent experiments. In Experiment 2, male rats were castrated and tested for the restoration of vocalizations. In one group, males were allowed to copulate freely; in the other, females had vaginal masks to prevent ejaculation, but not mounting. Vocalizations were restored only in males allowed to ejaculate. In Experiment 3, we measured vocalizations in sexually nai;ve and sexually experienced males following exposure to either castrated (CAS) males, testosterone (T)-treated males, ovariectomized (OVX) females, or OVX females receiving estrogen plus progesterone (E+P). Males vocalized most after exposure to E+P females, whether they were sexually experienced or naive. However, the rate of vocalizations was significantly higher after exposure to E+P females when the males were sexually experienced. In Experiment 4, we measured vocalizations in females following exposure to CAS males, T-treated males, OVX females, or E+P females. Females vocalized most after exposure to T-treated males. Our results show that (1) sexual experience facilitates vocalizations in male rats, (2) vocalizations are highest after exposure to hormonally receptive conspecifics, and (3) ultrasonic signaling is a sensitive index for assessing the hormonal disposition of conspecifics.