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Biomedical subjects

R Gandelman

Publications and source records attributed to R Gandelman.

At least 19 recordsLinked to original sources

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.

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Development of the surgically produced singleton mouse fetus.

All but one mouse embryo were removed from uteri on Day 8 of gestation and delivered via cesarean section on Day 18. Singletons were compared on various developmental indices to similarly delivered controls permitted to reside in uteri containing the normal complement of fetuses. The former were heavier at birth and weaning, had smaller ano-genital distance ratios (ano-genital distance/delivery weight), and displayed walking, gripping, eye-opening, and vaginal-opening earlier than controls. Singletons also exhibited greater durations and frequencies of various prenatal activities relative to controls when observed on Day 17 of gestation. Singleton status did not advance the onset of prenatal activity.

Animals↗

Uterine position and the activation of male sexual activity in testosterone propionate-treated female guinea pigs.

Fetal female guinea pigs were delivered surgically and their position within a uterine horn relative to male fetuses was noted. When adult they were ovariectomized, injected daily with testosterone propionate, and examined for male copulatory behaviors in response to the presence of a receptive female. Females that developed contiguous to a caudal male were functionally similar to those that had been situated between two males; both exhibited enhanced levels of mounting relative to females that were located contiguous to no males (with and without the presence of a caudal male) and to females contiguous to a cephalic male. Therefore, both contiguity and positioning of the male fetus are necessary conditions for prenatal masculinization of the female guinea pig. Lastly, four animals that had resided singly in the uterus displayed the lowest levels of copulatory behaviors.

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The expression of ano-genital distance data in the mouse.

Ano-genital distance (AGD) obtained from male and female mice at birth correlated significantly with body weight. Body length did not correlate significantly with AGD in females. Although it did so in the males, the coefficient accounted for less than half of the variance relative to that obtained by correlating AGD with weight. It is suggested that transformed AGD scores (AGD/body weight) rather than raw AGD data be analyzed when AGD is used to determine whether an independent variable that may affect body weight influences the prenatal hormone milieu.

Anal Canal↗

Singleton female mouse fetuses are subsequently unresponsive to the aggression-activating property of testosterone.

Eight-day pregnant mice were surgically prepared so that they carried a single fetus which was delivered by cesarean section on Day 18, one day prior to term. Other animals were permitted to carry their entire complement of fetuses which also were delivered surgically. Their position within a uterine horn relative to one another was noted. Adult ovariectomized testosterone-treated females that had been situated in utero contiguous to no male fetuses attacked an olfactory bulbectomized adult stimulus male. In contrast, females that resided singly in the uterus were unresponsive to the hormone; they displayed no aggressive behavior. Masculinization, therefore, appears to occur in utero in the absence of contiguity to male fetuses.

Aggression↗

Lever pressing for pups: evidence for hormonal influence upon maternal behavior of mice.

Five experiments were performed to determine the extent to which hormones influence maternal behavior of the female mouse. The number of pup-reinforced lever presses served as the measure of maternal behavior. In Experiment 1 it was found that postpartum mice performed significantly more pup-reinforced lever presses than intact or ovariectomized virgins. The second experiment showed that the augmentation of responding was unique to the postpartum period since responding was not facilitated during the last three days of pregnancy. Experiment 3 established that the postpartum augmentation of responding was mediated by the termination of pregnancy and not by parturition per se. It also was observed that the earlier during gestation pregnancy was terminated the greater the decline in response rate. Experiment 4 proved that ovarian secretions play a critical role in the pregnancy-terminated facilitation of pup-reinforced lever pressing. The final experiment demonstrated that the termination-of-pregnancy effect on responding in all likelihood is mediated by the synergistic actions of estrogen stimulation and progesterone withdrawal. The results show that the maternal behavior of the mouse, like that of the rat, is responsive to hormonal stimulation.

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Endocrine induction of intermale aggression in mice: a comparison of hormonal regimens and their relationship to naturally occurring behavior.

The level of intermale-like fighting behavior induced in female mice by various regimens of gonadal hormones known to establish aggression was compared. Regardless of whether the animals were exposed to testosterone propionate on the day of birth, the highest aggression scores were observed following chronic testosterone exposure in adult life. Females so treated also exhibited significantly more aggression than intact males. The least effective regimen was neonatal exposure to estradiol benzoate followed by long-term exposure of the adult to testosterone. Lastly, while castrated adult males were less likely to display aggressive behavior, those that fought did so at a level comparable to that of intact males.

Aggression↗

Contiguity to males in utero affects avoidance responding in adult female mice.

Female mice that had been situated in utero between two female fetuses displayed higher levels of active avoidance responding in adult life than females that had been located between two male fetuses and males for whom uterine position was without effect. Uterine position, therefore, influences acquired as well as species-typical behaviors.

Androgens↗

Is testosterone metabolized to estrogen in the forebrain of the Rockland-Swiss mouse?

The nuclear uptake and retention of [3H]testosterone or one of its metabolites was examined in the Rockland-Swiss (R-S) mouse. Castrated male and female mice were injected with 0.2 microgram of testosterone [1,2,6,7-3H(N)] per 100 g body weight and killed 1.5 h later. The brains were removed and processed for autoradiography. A nuclear localization of [3H]testosterone or one of its metabolites was found in the nucleus (n.) interstitialis striae terminalis and the n. amygdaloideus medialis. This localization is very different from that reported in another strain of mouse after the injection of [3H]dihydrotestosterone. Together with previous reports, these data suggest: (1) that aromatization of T to E2 in the forebrain of the R-S mouse is of minimal consequence; (2) there may be differences in uptake of T or its metabolites in different strains of mice; and (3) different androgens may exhibit unique patterns of nuclear uptake and retention.

Aggression↗

Deleterious effects of prenatal prednisolone exposure upon morphological and behavioral development of mice.

The influence of prenatal exposure to the synthetic glucocorticoid prednisolone (PRED) was examined in female offspring of mice administered the drug on Days 13-18 of pregnancy. The offspring weighed significantly less than control animals at birth and weaning. Animals born of mothers given the highest dosage of the drug (400 microgram) weighed less than controls in adulthood. Fetal exposure to PRED also resulted in morphological masculinization as evidenced by an increase in anogenital distance. In addition to its marked influence, prenatal PRED exposure retarded the attainment of the developmental milestones of eye opening, lifting, walking, and gripping. The effect of PRED upon the fetus is relatively rapid in that a reduction of fetal weight was observed in 13-day-old conceptae 7.5 hr following a maternal injection of PRED. The administration of an antiestrogenic compound (MER-25) concurrently with PRED prevented the reduction in birth weight, thereby suggesting that PRED acts, in part, by its known attenuation of fetoneonatal estrogen-binding protein. And finally, fetal exposure to PRED had virtually no effect upon reproductive competence as assessed by proportion of successful pregnancies, lactation performance, and postpartum fighting behavior. It is concluded that prenatal exposure to PRED markedly affects somatic and muscular/motor development and it may be worthwhile to examine the influence of the drug upon levels of gonadal hormones in an attempt to elucidate the mechanism through which its effects are produced.

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