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Biomedical subjects

N G Simon

Publications and source records attributed to N G Simon.

18 recordsLinked to original sources
PubMed1992

An assessment of agonist/antagonist effects of tamoxifen in the female mouse brain.

Ovariectomized CFW mice were treated with tamoxifen (TAM) alone or in combination with estradiol benzoate (EB) to determine its ability to promote/block lordotic behavior and the induction of hypothalamic progestin receptors (PR). Across a range of doses, TAM plus progesterone treatment did not activate female sexual behavior. When given with EB, TAM suppressed lordotic behavior in a dose-dependent fashion. TAM did not induce PR when given alone and it completely blocked the ability of EB to induce PR. It therefore appears that for these responses TAM functioned as a pure antagonist in the female mouse brain, although the degree of its antiestrogenicity varied with the response under consideration. A potential mechanism mediating this differential effectiveness is discussed.

Animals↗
PubMed1992

Genotype, uterine position, and testosterone sensitivity in older female mice.

CF-1 and CK (C57BL/6J x AKr) female mice that developed in utero between two males (2M), adjacent to one male (1M), or between two females (0M) were tested for their sensitivity to the aggression-promoting property of testosterone (T) beginning at 9 months of age. Comparisons between the strains showed that a higher proportion of CF-1 females fought in response to T and that the period of hormone exposure required to induce aggression also was shorter in this strain. Within each of the genotypes, there were no systematic differences in responsiveness to T related to contiguity to males during fetal development. While the results provide further evidence for genotype as a major influence on neural sensitivity to androgen, they do not support uterine position of females relative to males as a source of phenotypic variation in responsiveness.

Aggression↗
PubMed1991

In utero contiguity to males does not influence morphology, behavioral sensitivity to testosterone, or hypothalamic androgen binding in CF-1 female mice.

Physiological and behavioral systems presumably influenced by prenatal exposure to testosterone (T) were compared in CF-1 female mice from known uterine positions. Anogenital distance did not differ among females that developed in utero between two females (0M), adjacent to one male (1M), or between two males (2M) at birth, at weaning on Day 21, or on Day 60 postpartum. The age of vaginal opening and mean estrous cycle length also were similar among the groups. When ovariectomized and implanted with a T-containing silastic capsule, the mean number of days of treatment required to activate male-like aggressive behavior also did not differ among the three positional classifications. Finally, androgen binding in combined hypothalamic-preoptic-septal cytosol was assessed after 8 days of T treatment, and no systematic variation in [3H]DHT binding related to uterine position was found. These results indicate that contiguity to male fetuses did not induce variation among CF-1 females in morphological, behavioral, or biochemical systems thought to be influenced by prenatal exposure to T.

Aggression↗
PubMed1991

Timing of neonatal testosterone exposure in the differentiation of estrogenic regulatory systems for aggression.

Neonatal female CF-1 mice were exposed to testosterone (T) or oil vehicle on Days 1-3, 4-6, or 7-9 postpartum and were tested for the display of male-like aggressive behavior in response to diethylstilbestrol (DES) after ovariectomy during adulthood. The results showed that only the Day 1-3 T treatment established the capacity to exhibit fighting behavior following estrogen administration. These data suggest that sexual differentiation of an estrogen-responsive regulatory system for aggressive behavior occurs during a highly restricted period early in life.

Aggression↗
PubMed1990

Genetic variation in hypothalamic methyltrienolone (R1881) binding in male mice.

Methyltrienolone (R1881) binding to androgen receptors (AR) from combined hypothalamic-preoptic-septal cytosol was examined in CF-1, CFW, and CD-1 male mice, strains that differ in their sensitivity to the aggression-promoting property of this hormone. Both the affinity of R1881-AR binding and the number of binding sites (Bmax) significantly differed among the genotypes. The dissociation constant (Kd) was lower in CF-1 males (6.7 nM), a behaviorally responsive strain, in comparison to the insensitive CFW and CD-1 males (3.0 nM and 2.0 nM, respectively). The number of binding sites was higher in CF-1 and CFW males (9.07 and 8.81 fmol/mg protein, respectively) than in CD-1 males (5.11 fmol). The results were basically consistent with studies of neural dihydrotestosterone (DHT) binding in these genotypes, and the implications and limits of these data for understanding the androgenic regulation of intermale aggression are discussed.

Animals↗
PubMed1988

Medroxyprogesterone acetate and tamoxifen do not decrease aggressive behavior in CF-1 male mice.

Intact CF-1 male mice were given daily injections of either medroxyprogesterone acetate (MPA, an antiandrogen), tamoxifen (TAM, an antiestrogen), or the two drugs in combination and tested for aggressive behavior toward bulbectomized stimulus males. None of the treatments decreased fighting behavior over a 20-day test period and the presence of TAM led to increased aggression even in the presence of MPA. Testis weight was reduced by MPA while both compounds decreased seminal vesicle weight. The mechanisms involved in the observed effects are considered as well as the implications of the results for the clinical use of these compounds as modulators of testosterone-facilitated behaviors.

Aggression↗
PubMed1987

Sexual differentiation of androgen-sensitive and estrogen-sensitive regulatory systems for aggressive behavior.

CF-1 female mice were treated with either testosterone (T), diethylstilbestrol (DES), or methyltrienolone (R1881) on the day of birth and were subsequently tested for their responsiveness to the aggression-promoting property of androgen or estrogen during adulthood. The results showed that neonatal exposure to androgen enhanced subsequent sensitivity to androgenic stimulation but did not alter responsiveness to estrogens. Neonatal estrogen treatment established the capacity to exhibit aggression in response to estrogenic stimulation in adulthood but had little effect on responsiveness to androgens. These data indicate that the androgenic and estrogenic metabolites of T have distinct roles in masculinization of the neural substrate for aggressive behavior.

Aggression↗
PubMed1987

Nonaromatizable androgens may stimulate a male mouse reproductive behavior by binding estrogen receptors.

Castrated DBA/2J male mice emitted 70 kHz vocalizations to female stimuli in response to 10 days of treatment with either testosterone (T, 300 micrograms/day), diethylstilbestrol (DES, 1 or 3 micrograms/day) or methyltrienolone (R1881, 900 micrograms/day). Lower dosages of R1881 (300 and 600 micrograms/day) and the oil vehicle were relatively ineffective in restoring vocalizations. The effects of these hormones on restoring seminal vesicle weight did not always parallel their effects upon behavior. In general T and R1881 (600 and 900 micrograms/day) were effective in restoring seminal vesicles while DES, the lowest dose of R1881 (300 micrograms/day), and the oil vehicle were ineffective. In receptor competition studies, R1881 pretreatment significantly reduced estrogen binding in hypothalamic-preoptic cytosol. In fact the most effective dose for restoring vocalizations (900 micrograms/day) reduced available estrogen binding sites by 91%. We propose that the male-typical vocalizations of mice may normally be stimulated through the activation of estrogen receptors following androgen aromatization and that the ability of a pharmacological dosage of R1881 (900 micrograms/day) to restore behavior may be due to interaction with estrogen receptors in the brain.

Androgens↗
PubMed1987

Activation of male-typical aggression by testosterone but not its metabolites in C57BL/6J female mice.

Ovariectomized adult C57BL/6J mice were exposed to androgens, estrogens, or combined androgen-estrogen treatments and tested for the display of male-typical aggressive behavior toward olfactory bulbectomized stimulus males. Among the androgenic treatments (testosterone, dihydrotestosterone, or methyltrienolone) only testosterone, which, in contrast to the other androgens, can be aromatized, activated fighting behavior. In the second experiment, estradiol benzoate (EB) was totally ineffective as an aggression-promoting compound. Lastly, combined EB+dihydrotestosterone also did not induce male-like aggression. These data suggest that T itself may be capable of promoting aggression without undergoing aromatization or 5 alpha-reduction.

Aggression↗
PubMed1986

On the expression of H-Y antigen in transsexuals.

Histocompatibility-Y (H-Y) antigen, the presumptive inducer of the mammalian testis, is present in the cells of normal males and not in the cells of normal females. Recent reports have implied that patients with transsexualism exhibit H-Y antigen phenotypes at variance with those of normal males and females and, thus, that H-Y serology might provide a tool for the diagnosis and study of the transsexual condition. We therefore evaluated blood and testicular cells from 21 male-to-female transsexuals using conventional and monoclonal H-Y antibodies. We found no evidence of abnormal H-Y phenotype. Five of the patients were interviewed postoperatively by two examiners and rated for the diagnosis of transsexualism. Three of the five were rated primary transsexual by one or both examiners, and two were rated secondary transsexual.

Adult↗
PubMed1985

Induction of male-typical aggression by androgens but not by estrogens in adult female mice.

Ovariectomized adult CF-1 female mice were implanted with silastic capsules containing either testosterone (T), dihydrotestosterone (DHT), methyltrienolone (R1881), estradiol (E2), diethylstilbestrol (DES), or oil vehicle and were tested for aggressive behavior. The androgenic treatments (T, DHT, R1881) were highly effective in promoting male-like aggression while the estrogens (DES, E2) were completely ineffective. Subsequent receptor-binding studies confirmed assumptions about the specificity of DES, DHT, and R1881 binding to estrogen and androgen receptors in mouse hypothalamus.

Aggression↗
PubMed1979

Prenatal exposure to testosterone and its precursors influences morphology and later behavioral responsiveness to testosterone of female mice.

Prenatal exposure to testosterone (T), dehydroepiandrosterone or progesterone significantly increased ano-genital distance of female mice. In addition, prenatal exposure to T or pregnenolone significantly reduced the duration of T exposure during adult life required to induce intraspecific fighting behavior. However, the most masculinized females, those exposed to T prenatally, still had significantly shorter ano-genital distances and required a longer exposure period to T in order to establish fighting than did prenatally oil-exposed male mice. Additional experiments revealed that pregnenolone augments later responsiveness to the aggression-promoting property of T only if it is administered during the prenatal period of development.

Aggression↗
PubMed1978

Prenatal exposure to prednisone in humans and animals retards intrauterine growth.

Prednisone treatment for infertility and subsequent pregnancy maintenance in humans resulted in a significant decrease in the birth weight of full-term infants and a marked increase in the percentage of newborn infants weighing 2500 grams or less, that is, "light for dates" in comparison to control offspring. A parallel experiment with mice indicated that the reduction of birth weight was caused by exposure to corticosteroids rather than to maternal disease or malfunction.

Animals↗
PubMed1978

Spontaneous pup-killing by mice in response to large litters.

Primiparous lactating nice mice whose young were removed on the day of parturition were presented with foster litters of either 12 or 16 day-old young. The adults spontaneously killed young during Day 3-7 of the lactation period, killing more in the 16-pup than in the 12-pup litter. The lactating animal appeared to select the young to be killed on the basis of body weight. It killed significantly more young that were in the bottom half than in the top half of the weight range for its particular litter.

Animal Nutritional Physiological Phenomena↗